Publications by authors named "Heidrun Behrendt"

126 Publications

Ragweed plants grown under elevated CO levels produce pollen which elicit stronger allergic lung inflammation.

Allergy 2020 Oct 9. Epub 2020 Oct 9.

Center of Allergy & Environment (ZAUM), Technical University of Munich (TUM) and Helmholtz Zentrum München, Munich, Germany.

Background: Common ragweed has been spreading as a neophyte in Europe. Elevated CO levels, a hallmark of global climate change, have been shown to increase ragweed pollen production, but their effects on pollen allergenicity remain to be elucidated.

Methods: Ragweed was grown in climate-controlled chambers under normal (380 ppm, control) or elevated (700 ppm, based on RCP4.5 scenario) CO levels. Aqueous pollen extracts (RWE) from control- or CO -pollen were administered in vivo in a mouse model for allergic disease (daily for 3-11 days, n = 5) and employed in human in vitro systems of nasal epithelial cells (HNECs), monocyte-derived dendritic cells (DCs), and HNEC-DC co-cultures. Additionally, adjuvant factors and metabolites in control- and CO -RWE were investigated using ELISA and untargeted metabolomics.

Results: In vivo, CO -RWE induced stronger allergic lung inflammation compared to control-RWE, as indicated by lung inflammatory cell infiltrate and mediators, mucus hypersecretion, and serum total IgE. In vitro, HNECs stimulated with RWE increased indistinctively the production of pro-inflammatory cytokines (IL-8, IL-1β, and IL-6). In contrast, supernatants from CO -RWE-stimulated HNECs, compared to control-RWE-stimulated HNECS, significantly increased TNF and decreased IL-10 production in DCs. Comparable results were obtained by stimulating DCs directly with RWEs. The metabolome analysis revealed differential expression of secondary plant metabolites in control- vs CO -RWE. Mixes of these metabolites elicited similar responses in DCs as compared to respective RWEs.

Conclusion: Our results indicate that elevated ambient CO levels elicit a stronger RWE-induced allergic response in vivo and in vitro and that RWE increased allergenicity depends on the interplay of multiple metabolites.
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http://dx.doi.org/10.1111/all.14618DOI Listing
October 2020

[Air pollution and atopic eczema : Systematic review of findings from environmental epidemiological studies].

Hautarzt 2019 Mar;70(3):169-184

Zentrum Allergie & Umwelt (ZAUM), Technische Universität und Helmholtz Zentrum München, München, Deutschland.

Background: Among the many risk factors for the development of atopic eczema (AE), the influence of air pollution has recently been discussed more often. A systematic review about this topic however is lacking.

Aims: Which effects of outdoor air pollution (particles, nitric oxides, sulfur dioxide, ozone or general traffic exhaust emissions) on AE can be demonstrated in a systematic analysis of available environmental epidemiologic studies?

Methods: All environmental epidemiologic studies on AE and air pollution found in the literature database PubMed were identified. The most important key figures of these studies were tabulated, the quality of evidence was graded and the studies described.

Results: A total of 57 studies were identified. Only one of the 15 cross-sectional studies with a large-scale exposure assessment found a significant association between AE and air pollution. In contrast 23 of 30 studies with small-scale exposure assessment found a significant association between AE and traffic related emissions-especially from trucks. Of the 30 studies, 14 were cohort studies (1 adult, 13 birth cohorts). The sole adult cohort found an association with intrinsic AE. In the East Asian cohorts (all published since 2015), an association between maternal exposure to traffic-related pollution and incidence of AE in the offspring was found. This was less clear in cohorts from Europe/US or simply not investigated. In 5/5 panel studies (all from South Korea), symptom severity of AE was found to be significantly and positively related to outdoor air pollution.

Conclusions: In a systematic analysis of environmental epidemiologic studies about air pollution and AE rather good evidence was found that, based on small-scale exposure measurements, especially truck traffic emissions increased AE prevalence, while large-scale exposure to larger particles (PM10) or SO was without effect. Considering pathophysiologic aspects traffic exhaust emissions seem to affect both skin barrier function and activation of immune responses.
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http://dx.doi.org/10.1007/s00105-018-4330-3DOI Listing
March 2019

Artemisia pollen is the main vector for airborne endotoxin.

J Allergy Clin Immunol 2019 01 9;143(1):369-377.e5. Epub 2018 Aug 9.

Center of Allergy & Environment (ZAUM), Member of the German Center for Lung Research (DZL), Technical University and Helmholtz Center Munich, Munich, Germany; Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland. Electronic address:

Background: Endotoxin (LPS) released from gram-negative bacteria causes strong immunologic and inflammatory effects and, when airborne, can contribute to respiratory conditions, such as allergic asthma.

Objectives: We sought to identify the source of airborne endotoxin and the effect of this endotoxin on allergic sensitization.

Methods: We determined LPS levels in outdoor air on a daily basis for 4 consecutive years in Munich (Germany) and Davos (Switzerland). Air was sampled as particulate matter (PM) greater than 10 μm (PM > 10) and PM between 2.5 and 10 μm. LPS levels were determined by using the recombinant Factor C assay.

Results: More than 60% of the annual endotoxin exposure was detected in the PM > 10 fraction, showing that bacteria do not aerosolize as independent units or aggregates but adhered to large particles. In Munich 70% of annual exposure was detected between June 12th and August 28th. Multivariate modeling showed that endotoxin levels could be explained by phenological parameters (ie, plant growth). Indeed, days with high airborne endotoxin levels correlated well with the amount of Artemisia pollen in the air. Pollen collected from plants across Europe (100 locations) showed that the highest levels of endotoxin were detected on Artemisia vulgaris (mugwort) pollen, with little on other pollen. Microbiome analysis showed that LPS concentrations on mugwort pollen were related to the presence of Pseudomonas species and Pantoea species communities. In a mouse model of allergic disease, the presence of LPS on mugwort pollen was needed for allergic sensitization.

Conclusions: The majority of airborne endotoxin stems from bacteria dispersed with pollen of only one plant: mugwort. This LPS was essential for inducing inflammation of the lung and allergic sensitization.
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http://dx.doi.org/10.1016/j.jaci.2018.05.040DOI Listing
January 2019

Cytochrome P450s in human immune cells regulate IL-22 and c-Kit via an AHR feedback loop.

Sci Rep 2017 03 9;7:44005. Epub 2017 Mar 9.

Center of Allergy &Environment (ZAUM), Member of the German Center for Lung Research (DZL), Technische Universität München/Helmholtz Center, Munich, Germany.

The mechanisms how environmental compounds influence the human immune system are unknown. The environmentally sensitive transcription factor aryl hydrocarbon receptor (AHR) has immune-modulating functions and responds to small molecules. Cytochrome P4501 enzymes (CYP1) act downstream of the AHR and metabolize small molecules. However, it is currently unknown whether CYP1 activity is relevant for immune modulation. We studied the interdependence of CYP1 and AHR in human primary immune cells using pharmacological methods. CYP1 inhibition increased the expression levels of the stem cell factor receptor (c-Kit) and interleukin (IL)-22 but decreased IL-17. Single cell analyses showed that CYP1 inhibition especially promoted CD4 helper T (Th) cells that co-express c-Kit and IL-22 simultaneously. The addition of an AHR antagonist reversed all these effects. In addition to T cells, we screened other human immune cells for CYP and found cell-specific fingerprints, suggesting that similar mechanisms are present in multiple immune cells. We describe a feedback loop yet unknown in human immune cells where CYP1 inhibition resulted in an altered AHR-dependent immune response. This mechanism relates CYP1-dependent metabolism of environmental small molecules to human immunity.
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http://dx.doi.org/10.1038/srep44005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343665PMC
March 2017

Comparison of molecular and extract-based allergy diagnostics with multiplex and singleplex analysis.

Allergo J Int 2015;24:46-53. Epub 2015 Mar 14.

University Freiburg Medical Center, Department of Exercise Medicine and Sport, University of Freiburg, Freiburg, Germany ; Department of Pneumology, University of Freiburg, Freiburg, Germany ; Department of Pneumology, Freiburg University Medical Center, Albert-Ludwigs-University, Freiburg, Germany.

Background: ImmunoCAP ISAC 112, is a commercially available molecular allergy IgE multiplex test. Data on the comparison of this rather novel test with extract-based as well as molecular ImmunoCAP singleplex IgE tests is missing.

Objective: To perform a comparison between the ISAC multiplex IgE assay and the ImmunoCAP singleplex test results.

Methods: Serum samples of 101 adults with grass pollen allergy were analysed for sIgE to 112 allergenic molecules represented on the ISAC test as well as to common atopy-related extract-based allergy tests with the ImmunoCAP System (house dust mite [d1], cat [e1], dog [e5], cow's milk [f2], hen's egg [f1], hazelnut [f17], celery [f85], [m6], as well as pollen from birch [t3], hazel [t4], mugwort [w6], and ragweed [w1]). Subsequently statistical analysis was performed with the Spearman rank correlation test and the Clopper-Pearson method in order to compare the ISAC multiplex results with the sIgE singleplex results.

Results: The positive percent agreements (PPA) and negative percent agreement (NPA) of corresponding allergens between the ISAC sIgE test and the extract-based singleplex ImmunoCAP results at cutoff 0.1 kUA/l varied between 60-100 % for PPA and 78-97 % for NPA.

Conclusion: When taking into account corresponding allergens molecular testing with the ISAC multiplex test correlates well with ImmunoCAP singleplex results.
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http://dx.doi.org/10.1007/s40629-015-0046-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4686215PMC
March 2015

Common ragweed (Ambrosia artemisiifolia L.): allergenicity and molecular characterization of pollen after plant exposure to elevated NO2.

Plant Cell Environ 2016 Jan 19;39(1):147-64. Epub 2015 Sep 19.

Institute of Biochemical Plant Pathology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, 85764, Germany.

Ragweed pollen is the main cause of allergenic diseases in Northern America, and the weed has become a spreading neophyte in Europe. Climate change and air pollution are speculated to affect the allergenic potential of pollen. The objective of this study was to investigate the effects of NO2 , a major air pollutant, under controlled conditions, on the allergenicity of ragweed pollen. Ragweed was exposed to different levels of NO2 throughout the entire growing season, and its pollen further analysed. Spectroscopic analysis showed increased outer cell wall polymers and decreased amounts of pectin. Proteome studies using two-dimensional difference gel electrophoresis and liquid chromatography-tandem mass spectrometry indicated increased amounts of several Amb a 1 isoforms and of another allergen with great homology to enolase Hev b 9 from rubber tree. Analysis of protein S-nitrosylation identified nitrosylated proteins in pollen from both conditions, including Amb a 1 isoforms. However, elevated NO2 significantly enhanced the overall nitrosylation. Finally, we demonstrated increased overall pollen allergenicity by immunoblotting using ragweed antisera, showing a significantly higher allergenicity for Amb a 1. The data highlight a direct influence of elevated NO2 on the increased allergenicity of ragweed pollen and a direct correlation with an increased risk for human health.
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http://dx.doi.org/10.1111/pce.12601DOI Listing
January 2016

Pectate lyase pollen allergens: sensitization profiles and cross-reactivity pattern.

PLoS One 2015 15;10(5):e0120038. Epub 2015 May 15.

Christian Doppler Laboratory for Allergy Diagnosis and Therapy, Department of Molecular Biology, University of Salzburg, Salzburg, Austria.

Background: Pollen released by allergenic members of the botanically unrelated families of Asteraceae and Cupressaceae represent potent elicitors of respiratory allergies in regions where these plants are present. As main allergen sources the Asteraceae species ragweed and mugwort, as well as the Cupressaceae species, cypress, mountain cedar, and Japanese cedar have been identified. The major allergens of all species belong to the pectate lyase enzyme family. Thus, we thought to investigate cross-reactivity pattern as well as sensitization capacities of pectate lyase pollen allergens in cohorts from distinct geographic regions.

Methods: The clinically relevant pectate lyase pollen allergens Amb a 1, Art v 6, Cup a 1, Jun a 1, and Cry j 1 were purified from aqueous pollen extracts, and patients' sensitization pattern of cohorts from Austria, Canada, Italy, and Japan were determined by IgE ELISA and cross-inhibition experiments. Moreover, we performed microarray experiments and established a mouse model of sensitization.

Results: In ELISA and ELISA inhibition experiments specific sensitization pattern were discovered for each geographic region, which reflected the natural allergen exposure of the patients. We found significant cross-reactivity within Asteraceae and Cupressaceae pectate lyase pollen allergens, which was however limited between the orders. Animal experiments showed that immunization with Asteraceae allergens mainly induced antibodies reactive within the order, the same was observed for the Cupressaceae allergens. Cross-reactivity between orders was minimal. Moreover, Amb a 1, Art v 6, and Cry j 1 showed in general higher immunogenicity.

Conclusion: We could cluster pectate lyase allergens in four categories, Amb a 1, Art v 6, Cup a 1/Jun a 1, and Cry j 1, respectively, at which each category has the potential to sensitize predisposed individuals. The sensitization pattern of different cohorts correlated with pollen exposure, which should be considered for future allergy diagnosis and therapy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0120038PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4433284PMC
March 2016

Variation of the group 5 grass pollen allergen content of airborne pollen in relation to geographic location and time in season.

J Allergy Clin Immunol 2015 Jul 6;136(1):87-95.e6. Epub 2015 May 6.

Interdepartmental Centre of Bioclimatology, University of Florence, Florence, Italy.

Background: Allergies to grass pollen are the number one cause of outdoor hay fever. The human immune system reacts with symptoms to allergen from pollen.

Objective: We investigated the natural variability in release of the major group 5 allergen from grass pollen across Europe.

Methods: Airborne pollen and allergens were simultaneously collected daily with a volumetric spore trap and a high-volume cascade impactor at 10 sites across Europe for 3 consecutive years. Group 5 allergen levels were determined with a Phl p 5-specific ELISA in 2 fractions of ambient air: particulate matter of greater than 10 μm in diameter and particulate matter greater than 2.5 μm and less than 10 μm in diameter. Mediator release by ambient air was determined in FcεRI-humanized basophils. The origin of pollen was modeled and condensed to pollen potency maps.

Results: On average, grass pollen released 2.3 pg of Phl p 5 per pollen. Allergen release per pollen (potency) varied substantially, ranging from less than 1 to 9 pg of Phl p 5 per pollen (5% to 95% percentile). The main variation was locally day to day. Average potency maps across Europe varied between years. Mediator release from basophilic granulocytes correlated better with allergen levels per cubic meter (r(2) = 0.80, P < .001) than with pollen grains per cubic meter (r(2) = 0.61, P < .001). In addition, pollen released different amounts of allergen in the non-pollen-bearing fraction of ambient air, depending on humidity.

Conclusion: Across Europe, the same amount of pollen released substantially different amounts of group 5 grass pollen allergen. This variation in allergen release is in addition to variations in pollen counts. Molecular aerobiology (ie, determining allergen in ambient air) might be a valuable addition to pollen counting.
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http://dx.doi.org/10.1016/j.jaci.2015.01.049DOI Listing
July 2015

Non-allergenic factors from pollen modulate T helper cell instructing notch ligands on dendritic cells.

World Allergy Organ J 2015 20;8(1). Epub 2015 Jan 20.

Institute of Environmental Medicine, UNIKA-T, medical faculty of the Technische Universität München, Augsburg, Germany ; CK-Care, Christine Kühne Center for Allergy Research and Education, Davos-Wolfgang, Switzerland ; Department of Dermatology and Allergy Biederstein, Technische Universität München, Munich, Germany.

Background: Pollen allergens are delivered to epithelial surfaces of the upper respiratory tract in conjunction with multiple endogenous adjuvants. We previously demonstrated pollen-mediated modulation of cytokine and chemokine production of dendritic cells, contributing to a Th2-dominated micromilieu. As T helper cell differentiation not only depends on dendritic cell-derived cytokines but also on cell-cell-contact mediated mechanisms, we studied the expression of notch ligands and myeloid differentiation primary response protein 88 (MyD88) in dendritic cells matured in the presence of aqueous birch pollen extracts and pollen-associated E1-phytoprostanes.

Methods: Human monocyte-derived dendritic cells were stimulated with aqueous birch pollen extracts in the absence or presence of lipopolysaccharide, and mRNA expression levels of notch ligands delta-1 and -4, jagged-1 and -2 and of myd88 were determined. Regulation of Delta-4 and MyD88 by aqueous pollen extracts was assessed on protein level. The contribution of notch signaling to T helper cell differentiation was analyzed in allogeneic T cell stimulation assays.

Results: In immature dendritic cells, stimulation with pollen extracts resulted in an induction of both delta and jagged notch ligands. The lipopolysaccharide-induced up-regulation of delta-1 and -4 and of myd88 was decreased by aqueous pollen extracts, whereas jagged expression was induced. Reduction of Delta-4 and MyD88 by aqueous pollen extracts was confirmed on protein level. The Th2-skewing activity was contained in a fraction of aqueous pollen extracts enriched for molecules <3 kDa and was distinct from the previously identified E1-phytoprostanes. Reduction of notch signaling in dendritic cells matured in the presence aqueous pollen extract leads to inhibition of IL-10 and to induction of IL-5 production in naïve T cells differentiated by these dendritic cells.

Conclusions: Pollen derived, non-allergenic factors reduce the dendritic cell's expression of Th1 instructing Delta-like notch ligands and of MyD88, thereby promoting Th2 skewing of T helper cell responses.
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http://dx.doi.org/10.1186/s40413-014-0054-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300172PMC
January 2015

(ragweed) in Germany - current presence, allergological relevance and containment procedures.

Allergo J Int 2015;24:108-120. Epub 2015 Jul 11.

Foundation German Pollen Information Service, Berlin, Germany.

(ragweed) is a neophyte in Europe and Germany, which originated from the United States of America. In the USA the rate of sensitization against ragweed equals that of grass pollen, and without containment the rate of allergic sensitizations against ragweed pollen will clearly increase. Currently, the most frequent sensitizations in Germany are against grass pollen, followed by sensitizations against house dust mite and birch pollen. Ragweed pollen evokes symptoms at about 10 pollen/m3, grass pollen at about 15 pollen/m3. These concentrations of ragweed pollen are only reached on limited occasions in Germany. Ragweed cross-reacts with mugwort () and a correct diagnosis is only feasible with the ragweed specific allergen Amb a 1. Due to cross reactivity with mugwort, new sensitizations against ragweed pollen are not needed to evoke allergic symptoms. The neophyte encounters an already mugwort-sensitized population, extends the pollen season and may provoke new sensitizations. Ragweed sensitizations are characterized by an increased tendency to also affect the lower airways, which is less with mugwort sensitizations. Thus containment of ragweed is needed. Ragweed seeds are imported or spread by contaminated bird feed, the transport of ragweed contaminated soil (also in tyre treads) and agricultural products from infested areas. States bordering on ragweed positive areas, like Brandenburg and Bavaria, are especially at risk and invasion is already underway. Ragweed seeds survive up to 40 years in soil, and so extended timescales for eradication and observations are needed. Germany is, compared to other countries like France (Rhone-Valley), Italy (Po-Valley), Ukraine and Hungary, limited in respect to ragweed infestation. Conditions in Germany are therefore favourable for the containment of ragweed. Switzerland implemented legislation against birdseed contamination by ragweed early during the plants expansion, and obligatory ragweed registration- and eradication showed that ragweed containment is possible. Without counter measures ragweed expansion in Germany will take place, resulting in more allergic disease. Considering the increasing number of allergic individuals, even without ragweed invasion, containment of the neophyte should be actively persued. Unfortunately, time is running out.
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http://dx.doi.org/10.1007/s40629-015-0060-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4861741PMC
July 2015

Effects of ultrafine particles on the allergic inflammation in the lung of asthmatics: results of a double-blinded randomized cross-over clinical pilot study.

Part Fibre Toxicol 2014 Sep 10;11:39. Epub 2014 Sep 10.

Fraunhofer Institute for Toxicology and Experimental Medicine, Nikolai-Fuchs-Str. 1a, 30625, Hannover, Germany.

Background: Epidemiological and experimental studies suggest that exposure to ultrafine particles (UFP) might aggravate the allergic inflammation of the lung in asthmatics.

Methods: We exposed 12 allergic asthmatics in two subgroups in a double-blinded randomized cross-over design, first to freshly generated ultrafine carbon particles (64 μg/m³; 6.1 ± 0.4 × 10⁵ particles/cm³ for 2 h) and then to filtered air or vice versa with a 28-day recovery period in-between. Eighteen hours after each exposure, grass pollen was instilled into a lung lobe via bronchoscopy. Another 24 hours later, inflammatory cells were collected by means of bronchoalveolar lavage (BAL). (

Trial Registration: NCT00527462) RESULTS: For the entire study group, inhalation of UFP by itself had no significant effect on the allergen induced inflammatory response measured with total cell count as compared to exposure with filtered air (p = 0.188). However, the subgroup of subjects, which inhaled UFP during the first exposure, exhibited a significant increase in total BAL cells (p = 0.021), eosinophils (p = 0.031) and monocytes (p = 0.013) after filtered air exposure and subsequent allergen challenge 28 days later. Additionally, the potential of BAL cells to generate oxidant radicals was significantly elevated at that time point. The subgroup that was exposed first to filtered air and 28 days later to UFP did not reveal differences between sessions.

Conclusions: Our data demonstrate that pre-allergen exposure to UFP had no acute effect on the allergic inflammation. However, the subgroup analysis lead to the speculation that inhaled UFP particles might have a long-term effect on the inflammatory course in asthmatic patients. This should be reconfirmed in further studies with an appropriate study design and sufficient number of subjects.
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http://dx.doi.org/10.1186/s12989-014-0039-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4354282PMC
September 2014

Ragweed (Ambrosia artemisiifolia) pollen allergenicity: SuperSAGE transcriptomic analysis upon elevated CO2 and drought stress.

BMC Plant Biol 2014 Jun 27;14:176. Epub 2014 Jun 27.

Institute of Biochemical Plant Pathology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.

Background: Pollen of common ragweed (Ambrosia artemisiifolia) is a main cause of allergic diseases in Northern America. The weed has recently become spreading as a neophyte in Europe, while climate change may also affect the growth of the plant and additionally may also influence pollen allergenicity. To gain better insight in the molecular mechanisms in the development of ragweed pollen and its allergenic proteins under global change scenarios, we generated SuperSAGE libraries to identify differentially expressed transcripts.

Results: Ragweed plants were grown in a greenhouse under 380 ppm CO2 and under elevated level of CO2 (700 ppm). In addition, drought experiments under both CO2 concentrations were performed. The pollen viability was not altered under elevated CO2, whereas drought stress decreased its viability. Increased levels of individual flavonoid metabolites were found under elevated CO2 and/or drought. Total RNA was isolated from ragweed pollen, exposed to the four mentioned scenarios and four SuperSAGE libraries were constructed. The library dataset included 236,942 unique sequences, showing overlapping as well as clear differently expressed sequence tags (ESTs). The analysis targeted ESTs known in Ambrosia, as well as in pollen of other plants. Among the identified ESTs, those encoding allergenic ragweed proteins (Amb a) increased under elevated CO2 and drought stress. In addition, ESTs encoding allergenic proteins in other plants were also identified.

Conclusions: The analysis of changes in the transcriptome of ragweed pollen upon CO2 and drought stress using SuperSAGE indicates that under global change scenarios the pollen transcriptome was altered, and impacts the allergenic potential of ragweed pollen.
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http://dx.doi.org/10.1186/1471-2229-14-176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4084800PMC
June 2014

Surface modifications of silica nanoparticles are crucial for their inert versus proinflammatory and immunomodulatory properties.

Int J Nanomedicine 2014 5;9:2815-32. Epub 2014 Jun 5.

Center of Allergy and Environment (ZAUM), Technische Universität and Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.

Background: Silica (SiO₂) nanoparticles (NPs) are widely used in diverse industrial and biomedical applications. Their applicability depends on surface modifications, which can limit potential health problems.

Objective: To assess the potential impact of SiO₂ NP exposure and NPs chemical modifications in allergic airway inflammation.

Methods: Mice were sensitized by five repetitive intraperitoneal injections of ovalbumin/aluminum hydroxide (1 μg) over 42 days, then intratracheally instilled with plain or modified SiO₂ NPs (50 μg/mouse), and subsequently aerosol challenged for 20 minutes with ovalbumin. One or 5 days later, allergic inflammation was evaluated by cell differentiation of bronchoalveolar lavage fluid, lung function and gene expression and histopathology, as well as electron and confocal microscopy of pulmonary tissue.

Results: Plain SiO₂ NPs induced proinflammatory and immunomodulatory effects in vivo, highlighted by enhanced infiltration of inflammatory cells in the bronchoalveolar lavage fluid, induction of a pulmonary T helper type 2 (Th2) cytokine pattern, differentiation of type 2 macrophages, and by morphological changes in the lung of sensitized mice. These effects were dramatically attenuated using surface-functionalized NPs with amino and phosphate groups, but not with polyethylene glycol. The role of macrophages in taking up SiO₂ NPs was confirmed by flow cytometry, confocal microscopy, and gene expression analysis.

Conclusion: Our data suggest that amino and phosphate surface modifications, but not polyethylene glycol (PEG), mitigate the proinflammatory and immunomodulatory effect of SiO₂ NPs in allergic airway inflammation, paving the way for new strategies in the production of nanomaterials with lower health impact for humans.
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http://dx.doi.org/10.2147/IJN.S57396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4051720PMC
December 2014

Environmental pollution and allergy: historical aspects.

Chem Immunol Allergy 2014 22;100:268-77. Epub 2014 May 22.

Center for Allergy and Environment (ZAUM), Munich, Germany.

It may be a coincidence, but it is a fact that the first clear characterization of hay fever began in England where modern industrialization started in Europe. Only at the end of the 20th century were associations of the increasing prevalence of allergy with outdoor air pollution discussed. The seminal study came from Japan from the group of T. Miyamoto linking the increase in Japanese cedar pollinosis to an increased prevalence of Diesel cars and probably exposure to Diesel exhaust in epidemiological, animal experimental and in vitro studies. In Germany first epidemiological studies were done in North Rhine-Westphalia and Bavaria in 1987 and 1988 showing a striking prevalence of allergic disease of up to 10-20% in preschool children. After German reunification the most surprising observation was a lower prevalence of hay fever in East German children compared to the West, although there was a much higher air pollution with SO2 and large particulate matter. Modern smog as found over West German cities most likely originating from traffic exhaust and consisting of fine and ultrafine particles was shown to be associated with higher incidence rates of allergy and allergic sensitization. In the 10 years after reunification there was a steep increase of allergy prevalence in East German children reaching almost the same level as in West Germany. Obviously, a multitude of lifestyle factors - beyond air pollution - may be involved in the explanation of this phenomenon. Surprisingly the skin manifestation of atopy, namely atopic eczema, was more frequent in East German children compared to the West, thus differing from airway allergy. Meanwhile in vitro studies and animal experiments have shown that a variety of air pollutants mostly from environmental tobacco smoke (indoors) and from traffic exhaust (outdoors) can stimulate immune cells inducing a Th2-dominated response besides their irritative effects. While 50 years ago in allergy textbooks a clear distinction was made between 'toxic' or 'allergic', the newly developed concept of allergotoxicology has stimulated research tremendously, meaning 'the investigation of effects of toxic substances upon the induction, elicitation and maintenance of allergic reactions'.
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http://dx.doi.org/10.1159/000359918DOI Listing
April 2015

Pollen and pollinosis.

Chem Immunol Allergy 2014 22;100:228-33. Epub 2014 May 22.

Research Unit Aerobiology and Pollen Information, Department of Oto-Rhino-Laryngology, Medical University of Vienna, Vienna, Austria.

Pollen grains only represent a small fraction of the total amount of the viable biological particles present in the air, but pollen are the most important aeroallergens in the outdoor environment. The analysis of pollen has traditionally been carried out by microscopy, which can be traced back to the 17th century. Modern advances in molecular analysis could improve information for allergy sufferers and health care professionals. Pollen allergy (pollinosis) was first described in the 19th century. The prevalence of respiratory diseases increased dramatically during the latter part of the 20th century and millions of individuals are now affected. A number of scientists devised equipment to examine airborne biological particles during the 19th century, but aerobiological monitoring only became standardized during the 20th century. Airborne pollen are routinely monitored in many parts of the world, such as North America and Europe, and the first limited network has also been created for monitoring airborne allergen concentrations. Monitoring of the environment is often based on a combination of measurements and model results. Source-based models can increase our knowledge of airborne pollen because they can explain situations and processes that are almost impossible to understand using observations alone.
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http://dx.doi.org/10.1159/000358743DOI Listing
April 2015

Influence of alpine mountain climate of Bavaria on patients with atopic diseases: studies at the Environmental Research Station Schneefernerhaus (UFS - Zugspitze) - a pilot study.

Clin Transl Allergy 2014 8;4:17. Epub 2014 May 8.

Department of Dermatology and Allergy Biederstein, Technical University Munich, Munich, Germany.

Mountain and maritime climate therapy takes advantage of specific climatic conditions to treat chronic allergic diseases. It was the aim of the study to investigate effects of a 5 day sojourn on atopic diseases at the highest German mountain. In this pilot study 18 patients with grass pollen-induced rhinoconjunctivitis, atopic ezcema or asthma and 11 non-allergic controls were included. Skin physiology parameters, changes of the respiratory and nasal functions, subjective symptoms and blood parameters were measured during a 5-day observation period in the Environmental Research Station Schneefernerhaus (UFS) at the moderate altitude mountain region (Zugspitze; 2650 m alt.) compared to a low altitude area (Munich; 519 m alt.). Several of the skin physiology parameters changed significantly during the observation period (decrease of skin hydration, increase of skin smoothness, skin roughness, skin scaliness and pH-value). In patients with atopic eczema, the SCORAD (Severity Scoring of Atopic Dermatitis) and the scores of the DIELH (Deutsches Instrument zur Erfassung der Lebensqualität bei Hauterkrankungen) did not change significantly. Histamine induced itch decreased significantly. Parameters of nasal function did not change significantly. Several lung parameters showed a slight, but statistically significant improvement (forced expiratory volume in one second/volume capacity [FEV1/VC], peak expiratory flow [PEF], maximum expiratory flow at 50% of vital capacity [MEF 50], maximal mid-expiratory flow between 25% and 75% of vital capacity [MMFEF 25/75]), whereas the vital capacity (VC) decreased significantly. ECP (eosinophil cationic protein) in the serum and parameters of blood count changed significantly. These results show that the benefit of a moderate altitude mountain climate sojourn over a period of 5 days differs in depending on the atopic disease. Especially asthma parameters and itching of the skin improved. It would be interesting to assess the parameters during longer observation periods in alpine climate.
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http://dx.doi.org/10.1186/2045-7022-4-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4470350PMC
June 2015

High environmental ozone levels lead to enhanced allergenicity of birch pollen.

PLoS One 2013 20;8(11):e80147. Epub 2013 Nov 20.

ZAUM - Center of Allergy & Environment, Member of the German Center for Lung Research (DZL), Technische Universität München/Helmholtz Center, Munich, Germany.

Background: Evidence is compelling for a positive correlation between climate change, urbanisation and prevalence of allergic sensitisation and diseases. The reason for this association is not clear to date. Some data point to a pro-allergenic effect of anthropogenic factors on susceptible individuals.

Objectives: To evaluate the impact of urbanisation and climate change on pollen allergenicity.

Methods: Catkins were sampled from birch trees from different sites across the greater area of Munich, pollen were isolated and an urbanisation index, NO2 and ozone exposure were determined. To estimate pollen allergenicity, allergen content and pollen-associated lipid mediators were measured in aqueous pollen extracts. Immune stimulatory and modulatory capacity of pollen was assessed by neutrophil migration assays and the potential of pollen to inhibit dendritic cell interleukin-12 response. In vivo allergenicity was assessed by skin prick tests.

Results: The study revealed ozone as a prominent environmental factor influencing the allergenicity of birch pollen. Enhanced allergenicity, as assessed in skin prick tests, was mirrored by enhanced allergen content. Beyond that, ozone induced changes in lipid composition and chemotactic and immune modulatory potential of the pollen. Higher ozone-exposed pollen was characterised by less immune modulatory but higher immune stimulatory potential.

Conclusion: It is likely that future climate change along with increasing urbanisation will lead to rising ozone concentrations in the next decades. Our study indicates that ozone is a crucial factor leading to clinically relevant enhanced allergenicity of birch pollen. Thus, with increasing temperatures and increasing ozone levels, also symptoms of pollen allergic patients may increase further.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0080147PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3835901PMC
September 2014

Reduced skin reactivity to vasoconstrictor and vasodilator substances in atopic eczema.

Eur J Dermatol 2013 Nov-Dec;23(6):812-9

Klinik und Poliklinik für Dermatologie und Allergologie am Biederstein Technische Universität München, Biedersteinerstraβe 29, D-80802 München, Germany.

Unlabelled: Atopic eczema is a common chronic inflammatory disease with itchy skin and altered skin reactions to acetylcholine and nicotinic acid compared to healthy non-atopic individuals.

Aim: The aim of this study was to evaluate skin reactivity to 11 vasoactive substances and peptides by skin prick and intradermal tests in 20 patients with atopic eczema and 20 healthy controls.

Methods: Skin reactions, blanching, wheal and flare areas were measured by planimetry, 15 minutes after provocation.

Results: Patients with atopic eczema had significantly smaller reactions at certain concentrations of the vasodilators acetylcholine, bradykinin, calcitonin gene-related peptide, substance P and vasoactive intestinal peptide for flare, and of substance P and vasoactive intestinal peptide for wheals, in intradermal testing and/or in skin prick testing. Testing of the vasoconstrictors angiotensin-II, arginine-vasopressin, endothelin-1 and noradrenaline in atopic eczema resulted in significantly smaller reactions at certain concentrations for blanching in intradermal testing and/or skin prick testing. Significantly smaller reactions were seen with arginine-vasopressin for wheals and with arginine-vasopressin and noradrenaline for flares in intradermal testing and/or skin prick testing at certain concentrations. Significantly larger wheals were seen with angiotensin-II and endothelin-1 in intradermal testing and/or skin prick testing at certain concentrations. No significant differences were found for prostaglandin E2.

Conclusion: These results demonstrate not only a reduced responsiveness to vasodilators but also to vasoconstrictor substances and peptides in patients with atopic eczema, which may be considered a general feature of atopic eczema skin.
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http://dx.doi.org/10.1684/ejd.2013.2191DOI Listing
February 2015

Meta-analysis of air pollution exposure association with allergic sensitization in European birth cohorts.

J Allergy Clin Immunol 2014 Mar 4;133(3):767-76.e7. Epub 2013 Oct 4.

Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden.

Background: Evidence on the long-term effects of air pollution exposure on childhood allergy is limited.

Objective: We investigated the association between air pollution exposure and allergic sensitization to common allergens in children followed prospectively during the first 10 years of life.

Methods: Five European birth cohorts participating in the European Study of Cohorts for Air Pollution Effects project were included: BAMSE (Sweden), LISAplus and GINIplus (Germany), MAAS (Great Britain), and PIAMA (The Netherlands). Land-use regression models were applied to assess the individual residential outdoor levels of particulate matter with an aerodynamic diameter of less than 2.5 μm (PM2.5), the mass concentration of particles between 2.5 and 10 μm in size, and levels of particulate matter with an aerodynamic diameter of less than 10 μm (PM10), as well as measurement of the blackness of PM2.5 filters and nitrogen dioxide and nitrogen oxide levels. Blood samples drawn at 4 to 6 years of age, 8 to 10 years of age, or both from more than 6500 children were analyzed for allergen-specific serum IgE against common allergens. Associations were assessed by using multiple logistic regression and subsequent meta-analysis.

Results: The prevalence of sensitization to any common allergen within the 5 cohorts ranged between 24.1% and 40.4% at the age of 4 to 6 years and between 34.8% and 47.9% at the age of 8 to 10 years. Overall, air pollution exposure was not associated with sensitization to any common allergen, with odds ratios ranging from 0.94 (95% CI, 0.63-1.40) for a 1 × 10(-5) ∙ m(-1) increase in measurement of the blackness of PM2.5 filters to 1.26 (95% CI, 0.90-1.77) for a 5 μg/m(3) increase in PM2.5 exposure at birth address. Further analyses did not provide consistent evidence for a modification of the air pollution effects by sex, family history of atopy, or moving status.

Conclusion: No clear associations between air pollution exposure and development of allergic sensitization in children up to 10 years of age were revealed.
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http://dx.doi.org/10.1016/j.jaci.2013.07.048DOI Listing
March 2014

Molecular and immunological characterization of ragweed (Ambrosia artemisiifolia L.) pollen after exposure of the plants to elevated ozone over a whole growing season.

PLoS One 2013 18;8(4):e61518. Epub 2013 Apr 18.

Institute of Biochemical Plant Pathology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.

Climate change and air pollution, including ozone is known to affect plants and might also influence the ragweed pollen, known to carry strong allergens. We compared the transcriptome of ragweed pollen produced under ambient and elevated ozone by 454-sequencing. An enzyme-linked immunosorbent assay (ELISA) was carried out for the major ragweed allergen Amb a 1. Pollen surface was examined by scanning electron microscopy and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and phenolics were analysed by high-performance liquid chromatography. Elevated ozone had no influence on the pollen size, shape, surface structure or amount of phenolics. ATR-FTIR indicated increased pectin-like material in the exine. Transcriptomic analyses showed changes in expressed-sequence tags (ESTs), including allergens. However, ELISA indicated no significantly increased amounts of Amb a 1 under elevated ozone concentrations. The data highlight a direct influence of ozone on the exine components and transcript level of allergens. As the total protein amount of Amb a 1 was not altered, a direct correlation to an increased risk to human health could not be derived. Additional, the 454-sequencing contributes to the identification of stress-related transcripts in mature pollen that could be grouped into distinct gene ontology terms.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0061518PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3630196PMC
December 2013

Barrier responses of human bronchial epithelial cells to grass pollen exposure.

Eur Respir J 2013 Jul 8;42(1):87-97. Epub 2012 Nov 8.

Brooke Laboratory, Clinical and Experimental Sciences, Faculty of Medicine, University Hospital Southampton, Southampton, UK.

The airway epithelium forms a physical, chemical and immunological barrier against inhaled environmental substances. In asthma, these barrier properties are thought to be abnormal. In this study, we analysed the effect of grass pollen on the physical and immunological barrier properties of differentiated human primary bronchial epithelial cells. Following exposure to Timothy grass (Phleum pratense) pollen extract, the integrity of the physical barrier was not impaired as monitored by measuring the transepithelial resistance and immunofluorescence staining of tight junction proteins. In contrast, pollen exposure affected the immunological barrier properties by modulating vectorial mediator release. CXC chemokine ligand (CXCL)8/interleukin (IL)-8 showed the greatest increase in response to pollen exposure with preferential release to the apical compartment. Inhibition of the extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase pathways selectively blocked apical CXCL8/IL-8 release via a post-transcriptional mechanism. Apical release of CC chemokine ligand (CCL)20/macrophage inflammatory protein-3α, CCL22/monocyte-derived chemokine and tumour necrosis factor-α was significantly increased only in severe asthma cultures, while CCL11/eotaxin-1 and CXCL10/interferon-γ-induced protein-10 were reduced in nonasthmatic cultures. The bronchial epithelial barrier modulates polarised release of mediators in response to pollen without direct effects on its physical barrier properties. The differential response of cells from normal and asthmatic donors suggests the potential for the bronchial epithelium to promote immune dysfunction in asthma.
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http://dx.doi.org/10.1183/09031936.00075612DOI Listing
July 2013

Influence of dietary factors, age and nickel contact dermatitis on nickel excretion.

Contact Dermatitis 2012 Dec 29;67(6):351-8. Epub 2012 Aug 29.

ZAUM-Centre for Allergy and Environment, Munich D-80802, Germany.

Background: Nickel is a frequently detected cause of allergic contact dermatitis. Ingestion of nickel may lead to flares of nickel contact dermatitis.

Methods: We examined nickel excretion in the urine of 164 female patients with and without nickel contact dermatitis. The associations between age, atopic dermatitis, nickel contact dermatitis and nickel exposure through nutrition (e.g. dietary supplements) and by patch tests were investigated prospectively. Nickel was measured with atomic absorption spectrometry with two different standardized methods.

Results: A nickel detection limit of 0.2 µg/l was exceeded by all samples. The 95th percentiles of urine nickel concentration were 3.77 µg/l (age 18-30 years) and 3.98 µg/l (age 31-46 years). Bivariate analyses pointed to significantly increased nickel excretion with increasing age, ingestion of dietary supplements, drinking of stagnant tap water, and consumption of nickel-rich food. In the multivariate analysis, age and dietary supplements remained significant predictors of high nickel excretion. A non-significant increase in the median concentration of nickel was observed after the administration of conventional nickel patch tests. Patients with atopic eczema showed urine nickel concentrations similar to those in non-atopic controls.

Conclusions: The 95th percentile of nickel excretion in our study population markedly exceeded the actual reference value of 3 µg/l. Age and consumption of dietary supplements are the most important predictors. The use of stagnant tap water and consumption of nickel-rich food contribute to the total load. These factors should be explicitly mentioned when allergic patients on a low-nickel diet are counselled. In contrast, existing nickel contact sensitization was not more frequent in subjects with higher nickel excretion. Nickel patch testing may cause transient minor systemic nickel exposure. The findings of this study extend our understanding and management of factors associated with nickel allergy.
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http://dx.doi.org/10.1111/j.1600-0536.2012.02153.xDOI Listing
December 2012

Airborne indoor particles from schools are more toxic than outdoor particles.

Am J Respir Cell Mol Biol 2012 Nov 16;47(5):575-82. Epub 2012 Aug 16.

Center of Allergy & Environment, Technische Universität München, Biedersteiner Strasse 29, 80802 Munich, Germany.

High concentrations of particulate matter (PM(10)) were measured in classrooms. This study addresses the hazard of indoor particles in comparison to the better-studied outdoor particles. Samples were taken from six schools during teaching hours. Genome-wide gene expression in human BEAS-2B lung epithelial cells was analyzed and verified by quantitative PCR. Polycyclic aromatic hydrocarbons, endotoxin, and cat allergen (Fel d 1) were analyzed by standard methods. Enhancement of allergic reactivity by PM(10) was confirmed in human primary basophils. Acceleration of human blood coagulation was determined with supernatants of PM(10)-exposed human peripheral blood monocytes. Indoor PM(10) induced serine protease inhibitor B2 (involved in blood coagulation) and inflammatory genes (such as CXCL6, CXCL1, IL6, IL8; all P < 0.001). Outdoor PM(10) induced xenobiotic metabolizing enzymes (cytochrome P450 [CYP] 1A1, CYP1B1, TIPARP; all P < 0.001). The induction of inflammatory genes by indoor PM(10) was explained by endotoxin (indoor 128.5 ± 42.2 EU/mg versus outdoor 13.4 ± 21.5 EU/mg; P < 0.001), the induction of CYP by outdoor polycyclic aromatic hydrocarbons (indoor 8.3 ± 4.9 ng/mg versus outdoor 16.7 ± 15.2 ng/mg; P < 0.01). The induction of serine protease inhibitor B2 was confirmed by a more rapid human blood coagulation (P < 0.05). Indoor PM(10) only affected allergic reactivity from human primary basophils from cat-allergic individuals. This was explained by varying Fel d 1 concentrations in indoor PM(10) (P < 0.001). Indoor PM(10), compared with outdoor PM(10), was six times higher and, on an equal weight basis, induced more inflammatory and allergenic reactions, and accelerated blood coagulation. Outdoor PM(10) had significantly lower effects, but induced detoxifying enzymes. Therefore, preliminary interventions for the reduction of classroom PM(10) seem reasonable, perhaps through intensified ventilation.
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http://dx.doi.org/10.1165/rcmb.2012-0139OCDOI Listing
November 2012

Ultrafine particles affect the balance of endogenous pro- and anti-inflammatory lipid mediators in the lung: in-vitro and in-vivo studies.

Part Fibre Toxicol 2012 Jul 18;9:27. Epub 2012 Jul 18.

Institute of Allergy Research, Helmholtz Zentrum/Technische Universität München, Helmholtz Zentrum München, German.

Background: Exposure to ultrafine particles exerts diverse harmful effects including aggravation of pulmonary diseases like asthma. Recently we demonstrated in a mouse model for allergic airway inflammation that particle-derived oxidative stress plays a crucial role during augmentation of allergen-induced lung inflammation by ultrafine carbon particle (UfCP) inhalation. The mechanisms how particle inhalation might change the inflammatory balance in the lungs, leading to accelerated inflammatory reactions, remain unclear. Lipid mediators, known to be immediately generated in response to tissue injury, might be strong candidates for priming this particle-triggered change of the inflammatory balance.

Methods: We hypothesize that inhalation of UfCP may disturb the balance of pro- and anti-inflammatory lipid mediators in: i) a model for acute allergic pulmonary inflammation, exposing mice for 24 h before allergen challenge to UfCP inhalation (51.7 nm, 507 μg/m3), and ii) an in-vitro model with primary rat alveolar macrophages (AM) incubated with UfCP (10 μg/1 x 106 cells/ml) for 1 h. Lungs and AM were analysed for pro- and anti-inflammatory lipid mediators, namely leukotriene B4 (LTB4), prostaglandin E2 (PGE2), 15(S)-hydroxy-eicosatetraenoic acid (15(S)-HETE), lipoxin A4 (LXA4) and oxidative stress marker 8-isoprostane by enzyme immunoassays and immunohistochemistry.

Results: In non-sensitized mice UfCP exposure induced a light non-significant increase of all lipid mediators. Similarly but significantly in rat AM all lipid mediators were induced already within 1 h of UfCP stimulation. Also sensitized and challenge mice exposed to filtered air showed a partially significant increase in all lipid mediators. In sensitized and challenged mice UfCP exposure induced highest significant levels of all lipid mediators in the lungs together with the peak of allergic airway inflammation on day 7 after UfCP inhalation. The levels of LTB4, 8-isoprostane and PGE2 were significantly increased also one day after UfCP exposure. Immunohistochemistry localized highest concentrations of PGE2 especially in AM one day after UfCP exposure.

Conclusion: Our results suggest that UfCP exposure affects the balance between pro- and anti-inflammatory lipid mediators. In allergic mice, where the endogenous balance of pro- and anti-inflammatory mediators is already altered, UfCP exposure aggravates the inflammation and the increase in anti-inflammatory, pro-resolving lipid mediators is insufficient to counterbalance the extensive inflammatory response. This may be a contributing mechanism that explains the increased susceptibility of asthmatic patients towards particle exposure.
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http://dx.doi.org/10.1186/1743-8977-9-27DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3508980PMC
July 2012

The hygiene hypothesis does not apply to atopic eczema in childhood.

Chem Immunol Allergy 2012 13;96:15-23. Epub 2012 Mar 13.

There is evidence that environmental factors are important for the development of eczema. Different mechanisms have been discussed in the literature, the best known of which is the hygiene hypothesis. However, epidemiological data give reason for questioning this hypothesis with regard to childhood eczema. We present results from two German birth cohort studies (LISAplus and GINIplus) concerning regional prevalence patterns of eczema and the association of eczema with day care center attendance and older siblings. Our findings are not in line with the hygiene hypothesis and question its validity with regard to eczema. It seems reasonable to assume that the effect of environmental factors is somehow disease-specific.
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http://dx.doi.org/10.1159/000331805DOI Listing
July 2012

Climate change, environment and allergy.

Chem Immunol Allergy 2012 13;96:7-14. Epub 2012 Mar 13.

Climate change with global warming is a physicometeorological fact that, among other aspects, will also affect human health. Apart from cardiovascular and infectious diseases, allergies seem to be at the forefront of the sequelae of climate change. By increasing temperature and concomitant increased CO(2) concentration, plant growth is affected in various ways leading to prolonged pollination periods in the northern hemisphere, as well as to the appearance of neophytes with allergenic properties, e.g. Ambrosia artemisiifolia (ragweed), in Central Europe. Because of the effects of environmental pollutants, which do not only act as irritants to skin and mucous membranes, allergen carriers such as pollen can be altered in the atmosphere and release allergens leading to allergen-containing aerosols in the ambient air. Pollen has been shown not only to be an allergen carrier, but also to release highly active lipid mediators (pollen-associated lipid mediators), which have proinflammatory and immunomodulating effects enhancing the initiation of allergy. Through the effects of climate change in the future, plant growth may be influenced in a way that more, new and altered pollens are produced, which may affect humans.
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http://dx.doi.org/10.1159/000331804DOI Listing
July 2012

The pollen enigma: modulation of the allergic immune response by non-allergenic, pollen-derived compounds.

Curr Pharm Des 2012 ;18(16):2314-9

Technische Universität and Helmholtz Zentrum München, Biedersteinerstr. 29, München, Germany.

The question what makes an allergen an allergen puzzled generations of researchers. Pollen grains of anemophilous plants are the most important allergen carriers in ambient air, and pollinosis is a highly prevalent multi-organ disease in civilized countries. In the past, research on the allergenicity of pollen has mainly focused on elucidating genetic predisposing factors and on defining certain structural characteristics of pollen derived allergens. Recently, studies extended to the analysis of non-allergenic, adjuvant mediators co-released from pollen. Besides active proteases and oxidases, extracts of pollen contain low molecular weight molecules like pollen-associated lipid mediators or adenosine exhibiting a potential to stimulate and modulate cultured human immune cells. This article reviews our current knowledge on non-allergenic, protein and non-protein compounds from pollen and their in vitro and in vivo effects on the allergic immune response. To ultimately judge the physiological relevance of these compounds, a systematic approach will be needed comparing their releasability, content and activity in different, allergenic and non-allergenic, pollen species. System biology such as proteome and metabolome analysis will be a useful future approach to better understand pollen biology.
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http://dx.doi.org/10.2174/138161212800166040DOI Listing
August 2012

Patient-doctor interaction, psychobehavioural characteristics and mental disorders in patients with suspected allergies: do they predict "medically unexplained symptoms"?

Acta Derm Venereol 2011 Oct;91(6):666-73

Department of Psychosomatic Medicine and Psychotherapy, Technische Universitaet Muenchen, Munich, Germany.

In approximately 20% of patients with suspected allergies, no organic symptom explanation can be found. Limited knowledge about patients with "medically unexplained symptoms (MUS)" contributes to them being perceived as "difficult" and being treated inadequately. This study examined the psychobehavioural characteristics of patients presenting for a diagnostic allergy work-up. Patients were interviewed and completed various self-rating questionnaires. Patient-Doctor interaction was evaluated, and the organic explicability of the patients' symptoms was rated by allergists. Patients with vs. those without MUS differed in several respects. Mental comorbidity, female sex, dissatisfaction with care, and a problematic countertransference (the interviewer's feelings towards the patient) independently predicted MUS. Patients whose symptoms could be explained organically reported more psychobehavioural problems than a control group of immuno-therapy patients. There were no differences in patient-doctor interaction. In patients with suspected allergies, recognition of psychological burden and concurrent mental disorders is important. Mental comorbidity and a difficult patient-doctor interaction may predict MUS.
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http://dx.doi.org/10.2340/00015555-1147DOI Listing
October 2011

IL-22 and TNF-α represent a key cytokine combination for epidermal integrity during infection with Candida albicans.

Eur J Immunol 2011 Jul 20;41(7):1894-901. Epub 2011 May 20.

ZAUM-Center for Allergy and Environment, Technische Universität and Helmholtz Center Munich, Munich, Germany.

T cells exercise their full impact on target cells through a combination of secreted cytokines. The recently described T helper cell subset Th22 is characterized by a combinatorial secretion of IL-22 and TNF-α. Here, we demonstrate that IL-22 increases the TNF-α-dependent induction and secretion of several immune-modulatory molecules such as initial complement factors C1r and C1s, antimicrobial peptides S100A7 and HBD-2 (human β defensin 2), and antimicrobial chemokines CXCL-9/-10/-11 in primary human keratinocytes. The synergism of IL-22 and TNF-α is transmitted intracellularly by MAP kinases and downstream by transcription factors of the AP-1 family. The induction of innate immunity is relevant in an in vitro infection model, where keratinocytes stimulated with Th22 supernatants or recombinant IL-22 plus TNF-α effectively inhibit the growth of Candida albicans and maintain survival of epithelia. Accordingly, the combinatorial stimulation of keratinocytes with IL-22 and TNF-α most efficiently conserves the integrity of the epidermal barrier in a three-dimensional skin infection model as compared with IFN-γ, IL-17, IL-22 or TNF-α alone. In summary, we demonstrate that IL-22 and TNF-α represent a potent, synergistic cytokine combination for cutaneous immunity.
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http://dx.doi.org/10.1002/eji.201041197DOI Listing
July 2011

Effect of acupuncture on allergen-induced basophil activation in patients with atopic eczema:a pilot trial.

J Altern Complement Med 2011 Apr 28;17(4):309-14. Epub 2011 Mar 28.

Department of Dermatology and Allergy, Technische Universität München, Biedersteiner Straße 29, Munich, Germany.

Objective And Methods: The crucial symptom of atopic eczema is itch. Acupuncture has been shown to exhibit a significant effect on experimental itch; however, studies focusing on clinical itch in atopic eczema and corresponding mechanisms are lacking. The study design was a unicenter, single-blinded (observer), prospective, randomized clinical pilot trial with an additional experimental part. In 10 patients with atopic eczema, we investigated the effect of acupuncture treatment (n = 5) compared to no treatment (n = 5) on itch intensity and in vitro basophil CD63 expression upon allergen stimulation (house dust mite and timothy grass pollen) in a pilot trial.

Results: Mean itch intensity in a visual analog scale was rated significantly lower in the acupuncture group (-25% ± 26% [day 15-day 0]; -24% ± 31% [day 33-day 0]) than in the control group (15% ± 6% [day 15-day 0]; 29% ± 9% [day 33-day 0]). From day 0 (before treatment) to day 15 (after 5 acupuncture treatments) as well as day 33 (after 10 acupuncture treatments), the acupuncture group showed less CD63 positive basophils than the control group regarding stimulation with house dust mite and grass pollen allergen at various concentrations (5 ng/mL, 1 ng/mL, 0.5 ng/mL, or 0.25 ng/mL).

Conclusions: Our results show a reduction of itch intensity and of in vitro allergen-induced basophil activation in patients with atopic eczema after acupuncture treatment. Reducing basophil activation can be a further tool in investigating the mechanisms of action of acupuncture in immunoglobulin E-mediated allergy. Due to the limited number of patients included in our pilot trial, further studies are needed to strengthen the hypothesis.
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http://dx.doi.org/10.1089/acm.2009.0684DOI Listing
April 2011