Publications by authors named "Anna Erdei"

109 Publications

Robert B. Sim-Tribute.

Authors:
Anna Erdei

Viruses 2021 Aug 25;13(9). Epub 2021 Aug 25.

Department of Immunology, Eötvös Loránd University, 1053 Budapest, Hungary.

I met Bob in 1985, when I moved with my family to Oxford for a two-year EMBO fellowship at the MRC Immunochemistry Unit [...].
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http://dx.doi.org/10.3390/v13091681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472896PMC
August 2021

BCR activated CLL B cells use both CR3 (CD11b/CD18) and CR4 (CD11c/CD18) for adhesion while CR4 has a dominant role in migration towards SDF-1.

PLoS One 2021 20;16(7):e0254853. Epub 2021 Jul 20.

Department of Immunology, Eötvös Loránd University, Budapest, Hungary.

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia in the western world. In previous studies, various proportion of patients was found to carry CD11b+ or CD11c+ B cells whose presence was an unfavourable prognostic factor. The exact mechanism however, how these receptors contribute to the pathogenesis of CLL has not been revealed so far. Here we analysed the role of CD11b and CD11c on B cells of CLL patients in the adhesion to fibrinogen and in the migration towards stromal cell derived factor-1 (SDF-1) and studied the role of CR4 in the adherence of the CD11c+ B cell line BJAB. We observed that both CR3 and CR4 mediate adhesion of the malignant B cells. Moreover, we found, that CR4 was strongly involved in the migration of the leukemic cells towards the chemoattractant SDF-1. Our data suggest that CR3 and CR4 are not only passive markers on CLL B cells, but they might contribute to the progression of the disease. Since the role of SDF-1 is prominent in the migration of CLL cells into the bone marrow where their survival is supported, our findings help to understand how the presence of CD11c on leukemic B cells can worsen the prognosis of chronic lymphocytic leukaemia.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254853PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291664PMC
July 2021

Label-free real-time monitoring of the BCR-triggered activation of primary human B cells modulated by the simultaneous engagement of inhibitory receptors.

Biosens Bioelectron 2021 Nov 30;191:113469. Epub 2021 Jun 30.

Nanobiosensorics Laboratory, Institute of Technical Physics and Materials Science, Centre for Energy Research, 29-33 Konkoly-Thege Miklós út, Budapest, Hungary.

Today, there is an intense demand for lab-on-a-chip and tissue-on-a-chip applications in basic cell biological research and medical diagnostics. A particular challenge is the implementation of advanced biosensor techniques in point-of-care testing utilizing human primary cells. In this study, a resonant waveguide grating (RWG)-based label-free optical biosensor technique has been applied for real-time monitoring of the integrated responses of primary human tonsillar B cells initiated by B cell receptor (BCR) and modified by FcγRIIb and CR1 engagement. The BCR-triggered biosensor responses of resting and activated B cells were revealed to be specific and dose-dependent, in some cases with strong donor dependency. Targeted inhibition of Syk attenuated the label-free biosensor response upon BCR stimulation. Indifferent protein human serum albumin (HSA) did not interfere with the recorded signal to BCR stimulation. Simultaneous engagement of BCR and FcγRIIb modulated the kinetic signal of the cells. Activated and resting B cells exhibited different response profiles upon simultaneous engagement of BCR and CR1. This advanced approach has the potential to decipher interfering signaling events in human B cells, manage differences between activated and resting B cell states, helping to understand the actual integrated response of these immune cells, and could be useful in the point-of-care diagnostic testing on human primary cells.
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http://dx.doi.org/10.1016/j.bios.2021.113469DOI Listing
November 2021

New aspects in the regulation of human B cell functions by complement receptors CR1, CR2, CR3 and CR4.

Immunol Lett 2021 09 26;237:42-57. Epub 2021 Jun 26.

Department of Immunology, Eötvös Loránd University, Budapest, Hungary; MTA-ELTE Immunology Research Group, Eötvös Loránd University, Budapest, Hungary.

The involvement of complement in the regulation of antibody responses has been known for long. By now several additional B cell functions - including cytokine production and antigen presentation - have also been shown to be regulated by complement proteins. Most of these important activities are mediated by receptors interacting with activation fragments of the central component of the complement system C3, such as C3b, iC3b and C3d, which are covalently attached to antigens and immune complexes. This review summarizes the role of complement receptors interacting with these ligands, namely CR1 (CD35), CR2 (CD21), CR3 (CD11b/CD18) and CR4 (CD11c/CD18) expressed by B cells in health and disease. Although we focus on human B lymphocytes, we also aim to call the attention to important differences between human and mouse systems.
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http://dx.doi.org/10.1016/j.imlet.2021.06.006DOI Listing
September 2021

Autoantibodies Against the Complement Regulator Factor H in the Serum of Patients With Neuromyelitis Optica Spectrum Disorder.

Front Immunol 2021 27;12:660382. Epub 2021 Apr 27.

Department of Immunology, ELTE Eötvös Loránd University, Budapest, Hungary.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system (CNS), characterized by pathogenic, complement-activating autoantibodies against the main water channel in the CNS, aquaporin 4 (AQP4). NMOSD is frequently associated with additional autoantibodies and antibody-mediated diseases. Because the alternative pathway amplifies complement activation, our aim was to evaluate the presence of autoantibodies against the alternative pathway C3 convertase, its components C3b and factor B, and the complement regulator factor H (FH) in NMOSD. Four out of 45 AQP4-seropositive NMOSD patients (~9%) had FH autoantibodies in serum and none had antibodies to C3b, factor B and C3bBb. The FH autoantibody titers were low in three and high in one of the patients, and the avidity indexes were low. FH-IgG complexes were detected in the purified IgG fractions by Western blot. The autoantibodies bound to FH domains 19-20, and also recognized the homologous FH-related protein 1 (FHR-1), similar to FH autoantibodies associated with atypical hemolytic uremic syndrome (aHUS). However, in contrast to the majority of autoantibody-positive aHUS patients, these four NMOSD patients did not lack FHR-1. Analysis of autoantibody binding to FH19-20 mutants and linear synthetic peptides of the C-terminal FH and FHR-1 domains, as well as reduced FH, revealed differences in the exact binding sites of the autoantibodies. Importantly, all four autoantibodies inhibited C3b binding to FH. In conclusion, our results demonstrate that FH autoantibodies are not uncommon in NMOSD and suggest that generation of antibodies against complement regulating factors among other autoantibodies may contribute to the complement-mediated damage in NMOSD.
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http://dx.doi.org/10.3389/fimmu.2021.660382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111293PMC
October 2021

Revisiting the Coreceptor Function of Complement Receptor Type 2 (CR2, CD21); Coengagement With the B-Cell Receptor Inhibits the Activation, Proliferation, and Antibody Production of Human B Cells.

Front Immunol 2021 1;12:620427. Epub 2021 Apr 1.

Department of Immunology, Eötvös Loránd University, Budapest, Hungary.

The positive coreceptor function of complement receptor type 2 [CR2 (CD21)] on B cells is generally accepted, although its role in the enhancement of antibody production had only been proven in mice. The importance of this phenomenon prompted reinvestigation of the functional consequences of coclustering CD21 and the B cell receptor (BCR) on primary human cells. We found that, at non-stimulatory concentrations of anti-IgG/A/M, coclustering the BCR and CR2 enhanced the Ca response, while activation marker expression, cytokine production, proliferation, and antibody production were all inhibited upon the coengagement of CR2 and BCR on human B cells. Thus, the "textbook dogma" claiming that C3d acts as an adjuvant to enhance humoral immunity is relevant only to mice and not to humans.
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http://dx.doi.org/10.3389/fimmu.2021.620427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047317PMC
June 2021

Insect chemical ecology: chemically mediated interactions and novel applications in agriculture.

Arthropod Plant Interact 2020 Nov 9:1-14. Epub 2020 Nov 9.

Department of Plant Protection Biology, Swedish University of Agricultural Sciences, P.O. Box 102, 23053 Alnarp, Sweden.

Insect chemical ecology (ICE) evolved as a discipline concerned with plant-insect interactions, and also with a strong focus on intraspecific pheromone-mediated communication. Progress in this field has rendered a more complete picture of how insects exploit chemical information in their surroundings in order to survive and navigate their world successfully. Simultaneously, this progress has prompted new research questions about the evolution of insect chemosensation and related ecological adaptations, molecular mechanisms that mediate commonly observed behaviors, and the consequences of chemically mediated interactions in different ecosystems. Themed meetings, workshops, and summer schools are ideal platforms for discussing scientific advancements as well as identifying gaps and challenges within the discipline. From the 11th to the 22nd of June 2018, the 11th annual PhD course in ICE was held at the Swedish University of Agricultural Sciences (SLU) Alnarp, Sweden. The course was made up of 35 student participants from 22 nationalities (Fig. 1a) as well as 32 lecturers. Lectures and laboratory demonstrations were supported by literature seminars, and four broad research areas were covered: (1) multitrophic interactions and plant defenses, (2) chemical communication focusing on odor sensing, processing, and behavior, (3) disease vectors, and (4) applied aspects of basic ICE research in agriculture. This particular article contains a summary and brief synthesis of these main emergent themes and discussions from the ICE 2018 course. In addition, we also provide suggestions on teaching the next generation of ICE scientists, especially during unprecedented global situations.
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http://dx.doi.org/10.1007/s11829-020-09791-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650581PMC
November 2020

Activated Human Memory B Lymphocytes Use CR4 (CD11c/CD18) for Adhesion, Migration, and Proliferation.

Front Immunol 2020 29;11:565458. Epub 2020 Sep 29.

Department of Immunology, Eötvös Loránd University, Budapest, Hungary.

Complement receptors CR3 (CD11b/CD18) and CR4 (CD11c/CD18) of myeloid cells are known for long to participate in actin linked functions like phagocytosis, adhesion, and migration. The expression and role of these two β-integrins however, in human B lymphocytes have only scarcely been studied so far, although it has been shown recently that CD11c B cells are mainly memory cells. In our systematic study we investigated B cells isolated from tonsils and peripheral blood of healthy donors. We found, that while only 5% of resting tonsillar B cells expressed CD11c, their number increased up to 26% after 3 days of BCR stimulation. Lower, but still remarkable percentage of B lymphocytes were positive for CD11c after stimulation via TLR9 alone or via TLR9 and BCR simultaneously. At the same time, we detected no significant expression of CD11b on resting or activated tonsillar B cells. Blood B lymphocytes showed a similar expression pattern of both β-integrins. We demonstrated that CD11c molecules appearing on the surface of B cells are newly synthesized, reaching the number of 9,500 per activated B cell. We found that CR4 expressing B cells belong to the memory pool and the increase of CD11c expression on tonsillar B cells upon BCR mediated activation occurs parallel with class switching. Analysis of the function of CD11c revealed, that this β-integrin contributes to the adhesion and migration of activated B lymphocytes. We also demonstrated that the CR4 mediated adhesion promotes the proliferation of the BCR activated cells. Our studies are the first to demonstrate that CD11c expressed on BCR-activated human B cells are not only passive markers but functional drivers of memory B cell responses.
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http://dx.doi.org/10.3389/fimmu.2020.565458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550640PMC
May 2021

Fungal Volatiles as Olfactory Cues for Female Fungus Gnat, Lycoriella ingenua in the Avoidance of Mycelia Colonized Compost.

J Chem Ecol 2020 Oct 7;46(10):917-926. Epub 2020 Oct 7.

Department of Zoology, Plant Protection Institute, Centre for Agricultural Research, Eötvös Loránd Research Network, Budapest, Hungary.

The chemical signatures emitted by fungal substrates are key components for mycophagous insects in the search for food source or for suitable oviposition sites. These volatiles are usually emitted by the fruiting bodies and mycelia. The volatiles attract fungivorous insects, like flowers attract pollinators; certain flowers mimic the shape of mushroom fruiting bodies and even produce a typical mushroom odor to exploit on fungus-insect mutualism. There are numerous insects which are mycophagous or eat fungi additionally, but only a few are considered a threat in agriculture. Lycoriella ingenua is one of the most serious pests in mushroom cultivation worldwide. Here we attempt to examine the role of environmental volatiles upon behavioral oviposition preference. In two-choice bioassays, fungus gnats preferred uncolonized compost compared to colonized compost but preferred colonized compost against nothing. However, when colonized compost was paired against distilled water, no significant choice was observed. The comparison of fresh casing material and mycelium colonized casing material resulted in no significant preference. From colonized compost headspace, three antennally active volatiles were isolated by gas chromatography coupled with electroantennography and subsequently identified with gas chromatography coupled mass spectrometry as 1-hepten-3-ol, 3-octanone and 1-octen-3-ol. In behavioral assays the addition of said synthetic volatiles to uncolonized compost separately and in combination to mimic colonized compost resulted in avoidance. We thus partially elucidate the role of fungal volatiles in the habitat seeking behavior of Lycoriella ingenua.
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http://dx.doi.org/10.1007/s10886-020-01210-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547978PMC
October 2020

Novel opioid-neurotensin-based hybrid peptide with spinal long-lasting antinociceptive activity and a propensity to delay tolerance development.

Acta Pharm Sin B 2020 Aug 1;10(8):1440-1452. Epub 2020 May 1.

Department of Pharmacodynamics, Centre for Preclinical Research (CBP), Medical University of Warsaw, Warsaw 02-097, Poland.

The behavioral responses exerted by spinal administration of the opioid-neurotensin hybrid peptide, PK23, were studied in adult male rats. The antinociceptive effect upon exposure to a thermal stimulus, as well as tolerance development, was assessed in an acute pain model. The PK23 chimera at a dose of 10 nmol/rat produced a potent pain-relieving effect, especially after its intrathecal administration. Compared with intrathecal morphine, this novel compound was found to possess a favourable side effect profile characterized by a reduced scratch reflex, delayed development of analgesic tolerance or an absence of motor impairments when given in the same manner, though some animals died following barrel rotation as a result of its i.c.v. administration (in particular at doses higher than 10 nmol/rat). Nonetheless, these results suggest the potential use of hybrid compounds encompassing both opioid and neurotensin structural fragments in pain management. This highlights the enormous potential of synthetic neurotensin analogues as promising future analgesics.
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http://dx.doi.org/10.1016/j.apsb.2020.04.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488486PMC
August 2020

Essential Oil Headspace Volatiles Prevent Invasive Box Tree Moth () Oviposition-Insights from Electrophysiology and Behaviour.

Insects 2020 Jul 23;11(8). Epub 2020 Jul 23.

Zoology Department, Plant Protection Institute, Centre for Agricultural Research, 1022 Budapest, Hungary.

The box tree moth ( Walker) is an invasive species in Europe causing severe damage both in natural and ornamental boxwood ( spp.) vegetation. Pest management tactics are often based on the use of chemical insecticides, whereas environmentally-friendly control solutions are not available against this insect. The application of essential oils may provide effective protection against oviposition and subsequent larval damage. Oviposition deterrence of cinnamon, eucalyptus and lavender essential oils was tested on female in behavioural bioassays. Our results indicate that all the studied essential oils may be adequate deterrents; however, cinnamon oil exhibited the strongest effect. To determine the physiologically active compounds in the headspace of the essential oils, gas chromatography coupled with electroantennography recordings were performed in parallel with gas chromatography-mass spectrometry to identify the volatile constituents. In addition, the release rates of various components from vial-wick dispensers were measured during the oviposition bioassay. These results may serve as a basis for the development of a practical and insecticide-free plant protection method against this invasive moth species.
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http://dx.doi.org/10.3390/insects11080465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469176PMC
July 2020

The differential role of CR3 (CD11b/CD18) and CR4 (CD11c/CD18) in the adherence, migration and podosome formation of human macrophages and dendritic cells under inflammatory conditions.

PLoS One 2020 4;15(5):e0232432. Epub 2020 May 4.

MTA-ELTE Immunology Research Group, Eötvös Loránd University, Budapest, Hungary.

CR3 and CR4, the leukocyte specific β2-integrins, involved in cellular adherence, migration and phagocytosis, are often assumed to have similar functions. Previously however, we proved that under physiological conditions CR4 is dominant in the adhesion to fibrinogen of human monocyte-derived macrophages (MDMs) and dendritic cells (MDDCs). Here, using inflammatory conditions, we provide further evidence that the expression and function of CR3 and CR4 are not identical in these cell types. We found that LPS treatment changes their expression differently on MDMs and MDDCs, suggesting a cell type specific regulation. Using mAb24, specific for the high affinity conformation of CD18, we proved that the activation and recycling of β2-integrins is significantly enhanced upon LPS treatment. Adherence to fibrinogen was assessed by two fundamentally different approaches: a classical adhesion assay and a computer-controlled micropipette, capable of measuring adhesion strength. While both receptors participated in adhesion, we demonstrated that CR4 exerts a dominant role in the strong attachment of MDDCs. Studying the formation of podosomes we found that MDMs retain podosome formation after LPS activation, whereas MDDCs lose this ability, resulting in a significantly reduced adhesion force and an altered cellular distribution of CR3 and CR4. Our results suggest that inflammatory conditions reshape differentially the expression and role of CR3 and CR4 in macrophages and dendritic cells.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232432PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7197861PMC
July 2020

Utilization of complement receptors in immune cell-microbe interaction.

FEBS Lett 2020 08 12;594(16):2695-2713. Epub 2020 Feb 12.

MTA-ELTE Immunology Research Group, Eötvös Loránd University, Budapest, Hungary.

The complement system is a major humoral component of immunity and is essential for the fast elimination of pathogens invading the body. In addition to its indispensable role in innate immunity, the complement system is also involved in pathogen clearance during the effector phase of adaptive immunity. The fastest way of killing the invader is lysis by the membrane attack complex, which is formed by the terminal components of the complement cascade. Not all pathogens are lysed however and, if opsonized by a variety of molecules, they undergo phagocytosis and disposal inside immune cells. The most important complement-derived opsonins are C1q, the first component of the classical pathway, MBL, the initiator of the lectin pathway and C3-derived activation fragments, including C3b, iC3b and C3d, which all serve as ligands for their corresponding receptors. In this review, we discuss how complement receptors are utilized by various immune cells to tackle invading microbes, or by pathogens to evade host response.
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http://dx.doi.org/10.1002/1873-3468.13743DOI Listing
August 2020

Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition).

Eur J Immunol 2019 Oct;49(10):1457-1973

Flow Cytometry Laboratory, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München, German Research Center for Environmental Health, München, Germany.

These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
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http://dx.doi.org/10.1002/eji.201970107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350392PMC
October 2019

Complement Receptor Type 1 (CR1, CD35), the Inhibitor of BCR-Mediated Human B Cell Activation, Differentially Regulates TLR7, and TLR9 Induced Responses.

Front Immunol 2019 2;10:1493. Epub 2019 Jul 2.

MTA-ELTE Immunology Research Group, Eötvös Loránd University, Budapest, Hungary.

The complement system and Toll-like receptors (TLRs) are essential contributors of innate immunity. Separate activation of these systems has been shown to play a role in initiating and shaping the adaptive immune response, however the modulation of various B cell functions by the simultaneous involvement of these two systems has not yet been uncovered. We demonstrate here that occupancy of complement receptor type 1 (CR1, CD35) by its natural, complement component C3-derived ligand significantly and dose dependently reduces the TLR9-induced expression of activation markers, cytokine production, proliferation, and antibody production by human B cells, but has no effect on the TLR7-induced functions. The synergistic response to the simultaneous engagement of either TLR9 or TLR7 along with the BCR however, is significantly inhibited by CR1 occupancy. Our findings imply that both under physiological and pathological conditions, when complement- and TLR-activating microbial and damage products are present in the B cell environment, the cooperation between CR1 and TLR7 or TLR9 provides additional levels of the regulation of human B cell functions.
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http://dx.doi.org/10.3389/fimmu.2019.01493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6614493PMC
July 2020

Biochemical and pharmacological investigation of novel nociceptin/OFQ analogues and N/OFQ-RYYRIK hybrid peptides.

Peptides 2019 02 1;112:106-113. Epub 2018 Dec 1.

Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, H-6726 Szeged, Temesvári krt. 62., Hungary. Electronic address:

The endogenous ligand nociceptin (N/OFQ) and a positively charged synthetic peptide RYYRIK are both selective for the nociceptin opioid receptor (NOPr). Despite their structural dissimilarity, N/OFQ and RYYRIK compete for the same binding site of NOP receptor possessing full and partial agonistic character, respectively. In the view of the message-address concept, hybrid peptide constructs were probed for the NOP receptor combining different regions of N/OFQ and RYYRIK related peptide sequences. Nine novel nociceptin- or Ac-RYYRIK-NH peptide variants or hybrid peptides were synthesized and characterized. Peptides P2 and P8 contain fragments of native N/OFQ. The other seven analogues (P1, P3-7, P9) are composed of Ac-RYYRIK-NH fragments and parts of the original nociceptin sequence. The analogues were characterized in receptor binding assays and G-protein activation experiments on rat brain membranes, as well as by electrically stimulated mouse vas deferens bioassay. In receptor binding assays ligands P2, P4, P6 (K 0.37 nM) and P7 showed higher affinity (K 0.65 nM, 0.6 nM, 0.37 nM and 0.44 nM, respectively) for NOP receptor than their parent compounds N/OFQ (K 2.8 nM) or Ac-RYYRIK-NH (K 4.2 nM). In [S]GTPγS binding experiments P2 and P3 behaved as full agonists. The other variants exhibited partial agonist properties characterized by submaximal stimulatory effects. In mouse vas deferens bioassay only P2 showed agonist activity. P4, P5, P6 inhibited the biological activity of N/OFQ more effectively than the NOP receptor selective antagonist JTC-801. In summary, hybrid peptides P4, P5 and P6 proved to be NOP receptor partial agonists even antagonists, while P2 peptide retained the full agonist property.
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http://dx.doi.org/10.1016/j.peptides.2018.11.010DOI Listing
February 2019

Distinct UV-A or UV-B irradiation induces protochlorophyllide photoreduction and bleaching in dark-grown pea (Pisum sativum L.) epicotyls.

Photosynth Res 2019 Apr 17;140(1):93-102. Epub 2018 Sep 17.

Department of Plant Anatomy, Faculty of Science, Institute of Biology, ELTE Eötvös Loránd University, Pázmány P. s. 1/c, Budapest, 1117, Hungary.

The effects of distinct UV-A and UV-B radiations were studied on etiolated pea (Pisum sativum L.) epicotyls. Emission spectra of the native protochlorophyll and protochlorophyllide forms were measured when epicotyls were excited with 360 or 300 nm light. The UV-A (360 nm) excited mainly the non-enzyme-bound monomers of protochlorophyll and protochlorophyllide and the UV-B (300 nm) excited preferentially the flash-photoactive protochlorophyllide complexes. These latter complexes converted into short- and long-wavelength chlorophyllide forms at 10-s illumination with both wavelength irradiations. As the spectral changes were very small, the effects of longer illumination periods were studied. Room temperature fluorescence emission spectra were measured from the same epicotyl spots before and after irradiation with various wavelengths between 280 and 360 nm for 15 min and the "illuminated" minus "dark" difference spectra were calculated. Both the UV-A and the UV-B irradiations caused photoreduction of protochlorophyllide into chlorophyllide. At 10 µmol photons m s, the photoreduction rates were similar, however, at 60 µmol photons m s, the UV-B irradiation was more effective in inducing chlorophyllide formation than the UV-A. The action spectra of protochlorophyllide plus protochlorophyll loss and chlorophyllide production showed that the radiation around 290 nm was the most effective in provoking protochlorophyllide photoreduction and the UV light above 320 nm caused strong bleaching. These results show that the effect of the UV radiation should be considered when discussing the protochlorophyllide-chlorophyllide photoreduction during germination and as a part of the regeneration of the photosynthetic apparatus proceeding in the daily run of photosynthesis.
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http://dx.doi.org/10.1007/s11120-018-0584-yDOI Listing
April 2019

Identification of the Female-Produced Sex Pheromone of an Invasive Greenhouse Pest, the European Pepper Moth (Duponchelia fovealis).

J Chem Ecol 2018 Mar 29;44(3):257-267. Epub 2018 Jan 29.

Department of Zoology, Plant Protection Institute, Centre for Agricultural Research, Hungarian Academy of Sciences, Budapest, Hungary.

The European pepper moth (Duponchelia fovealis, Lepidoptera, Crambidae, Spilomelinae) is an invasive pest of greenhouses in many countries, causing serious damages to horticultural plants. Coupled gas chromatographic-electroantennographic detection analysis of the female gland extract revealed two antennally active peaks. Using coupled gas chromatography-mass spectrometry (GC-MS), one was identified as (Z)-11-hexadecenal (Z11-16:Ald); however, further analysis on different types of capillary columns indicated that the second active compound has two different isomers, (E)-13-octadecenal (E13-18:Ald) and (Z)-13-octadecenal (Z13-18:Ald). The approximate ratio of E13-18:Ald, Z13-18:Ald and Z11-16:Ald in the crude pheromone gland extract was 10:1:0.1, respectively. Single sensillum recordings showed that there was one sensory neuron that responded with a high amplitude spike to both E13-18:Ald and Z13-18:Ald, while another neuron housed in the same sensillum responded to Z11-16:Ald. Field evaluation of the identified compounds indicated that the E13-18:Ald was necessary to evoke the attraction of males; although the presence of Z13-18:Ald and Z11-16:Ald increased the catches in traps. The highest number of caught males was achieved when E13-18:Ald, Z13-18:Ald and Z11-16:Ald were present in baits in the same ratio as in the female gland extract. This pheromone can be used in a monitoring strategy and could potentially lead to the development of mating disruption.
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http://dx.doi.org/10.1007/s10886-018-0928-2DOI Listing
March 2018

Non-identical twins: Different faces of CR3 and CR4 in myeloid and lymphoid cells of mice and men.

Semin Cell Dev Biol 2019 01 24;85:110-121. Epub 2017 Nov 24.

MTA-ELTE Immunology Research Group, Department of Immunology, Eötvös Loránd University, Budapest, Hungary; Department of Immunology, Eötvös Loránd University, Budapest, Hungary.

Integrins are cell membrane receptors that are involved in essential physiological and serious pathological processes. Their main role is to ensure a closely regulated link between the extracellular matrix and the intracellular cytoskeletal network enabling cells to react to environmental stimuli. Complement receptor type 3 (CR3, αMβ, CD11b/CD18) and type 4 (CR4, αXβ, CD11c/CD18) are members of the β-integrin family expressed on most white blood cells. Both receptors bind multiple ligands like iC3b, ICAM, fibrinogen or LPS. β-integrins are accepted to play important roles in cellular adhesion, migration, phagocytosis, ECM rearrangement and inflammation. Several pathological conditions are linked to the impaired functions of these receptors. CR3 and CR4 are generally thought to mediate overlapping functions in monocytes, macrophages and dendritic cells, therefore the potential distinctive role of these receptors has not been investigated so far in satisfactory details. Lately it has become clear that a functional segregation has evolved between the two receptors regarding phagocytosis, cellular adhesion and podosome formation. In addition to their tasks on myeloid cells, the expression and function of CR3 and CR4 on lymphocytes have also gained interest recently. The picture is further complicated by the fact that while these β-integrins are expressed by immune cells both in mice and humans, there are significant differences in their expression level, functions and the pathological consequences of genetic defects. Here we aim to summarize our current knowledge on CR3 and CR4 and highlight the functional differences between these receptors, involving their expression in myeloid and lymphoid cells of both men and mice.
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http://dx.doi.org/10.1016/j.semcdb.2017.11.025DOI Listing
January 2019

Biochemical and pharmacological characterization of three opioid-nociceptin hybrid peptide ligands reveals substantially differing modes of their actions.

Peptides 2018 01 13;99:205-216. Epub 2017 Oct 13.

Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, H-6726, Szeged, Temesvári krt. 62., Hungary. Electronic address:

In an attempt to design opioid-nociceptin hybrid peptides, three novel bivalent ligands, H-YGGFGGGRYYRIK-NH, H-YGGFRYYRIK-NH and Ac-RYYRIKGGGYGGFL-OH were synthesized and studied by biochemical, pharmacological, biophysical and molecular modelling tools. These chimeric molecules consist of YGGF sequence, a crucial motif in the N-terminus of natural opioid peptides, and Ac-RYYRIK-NH which was isolated from a combinatorial peptide library as an antagonist or partial agonist that inhibits the biological activity of the endogenously occurring heptadecapeptide nociceptin. Solution structures for the peptides were studied by analysing their circular dichroism spectra. Receptor binding affinities were measured by equilibrium competition experiments using four highly selective radioligands. G-protein activating properties of the multitarget peptides were estimated in [S]GTPγS binding tests. The three compounds were also measured in electrically stimulated mouse vas deferens (MVD) bioassay. H-YGGFGGGRYYRIK-NH (BA55), carrying N-terminal opioid and C-terminal nociceptin-like sequences interconnected with GGG tripeptide spacer displayed a tendency of having either unordered or β-sheet structures, was moderately potent in MVD and possessed a NOP/KOP receptor preference. A similar peptide without spacer H-YGGFRYYRIK-NH (BA62) exhibited the weakest effect in MVD, more α-helical periodicity was present in its structure and it exhibited the most efficacious agonist actions in the G-protein stimulation assays. The third hybrid peptide Ac-RYYRIKGGGYGGFL-OH (BA61) unexpectedly displayed opioid receptor affinities, because the opioid message motif is hidden within the C-terminus. The designed chimeric peptide ligands presented in this study accommodate well into a group of multitarget opioid compounds that include opioid-non-opioid peptide dimer analogues, dual non-peptide dimers and mixed peptide- non-peptide bifunctional ligands.
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http://dx.doi.org/10.1016/j.peptides.2017.10.005DOI Listing
January 2018

Introduction.

Immunol Lett 2017 09;189

2017, Hungary.

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http://dx.doi.org/10.1016/j.imlet.2017.08.006DOI Listing
September 2017

Cyclic Biphalin Analogues Incorporating a Xylene Bridge: Synthesis, Characterization, and Biological Profile.

ACS Med Chem Lett 2017 Aug 12;8(8):858-863. Epub 2017 Jul 12.

Dipartimento di Farmacia, Università di Chieti-Pescara "G. d'Annunzio", Via dei Vestini 31, 66100 Chieti, Italy.

In this work we enhanced the ring lipophilicity of biphalin introducing a xylene moiety, thus obtaining three cyclic regioisomers. Novel compounds have similar activity as the parent compound, but one of these () shows a remarkable increase of antinociceptive effect. Nociception tests have disclosed its significant high potency and the more prolonged effect in eliciting analgesia, higher than that of biphalin and of the disulfide-bridge-containing analogue ().
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http://dx.doi.org/10.1021/acsmedchemlett.7b00210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5554896PMC
August 2017

Functional studies of chronic lymphocytic leukemia B cells expressing β-integrin type complement receptors CR3 and CR4.

Immunol Lett 2017 09 31;189:73-81. Epub 2017 May 31.

MTA-ELTE Immunology Research Group, Department of Immunology, Eötvös Loránd University, Budapest, Hungary; Department of Immunology, Eötvös Loránd University, Budapest, Hungary. Electronic address:

The expression and role of CR3 (CD11b/CD18) and CR4 (CD11c/CD18) in B cells are not yet explored in contrast to myeloid cells, where these β-integrin type receptors are known to participate in various cellular functions, including phagocytosis, adherence and migration. Here we aimed to reveal the expression and role of CR3 and CR4 in human B cells. In B cells of healthy donors CR3 and CR4 are scarcely expressed. However, two patients with chronic lymphocytic leukemia (CLL) characterized by a peculiar immune-phenotype containing both CD5-positive and CD5-negative B cell populations made possible to study these molecules in distinct B cell subsets. We found that CD11b and CD11c were expressed on both CD5-positive and CD5-negative B cells, albeit to different extents. Our data suggest that these receptors are involved in spreading, since this activity of CpG-activated B cells on fibrinogen could be partially blocked by monoclonal antibodies specific for CD11b or CD11c. CpG-stimulation lead to proliferation of both CD5-positive and CD5-negative B cells of the patients with a less pronounced effect on the CD5-positive cells. In contrast to normal B cells, CLL B cells of both patients reacted to CpG-stimulation with robust IL-10 production. The concomitant, suboptimal stimulus via the BCR and TLR9 exerted either a synergistic enhancing effect or resulted in inhibition of proliferation and IL-10 production of patients' B cells. Our data obtained studying B cells of leukemic patients point to the role of CR3 and probably CR4 in the interaction of tumor cells with the microenvironment and suggest the involvement of IL-10 producing B cells in the pathologic process.
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http://dx.doi.org/10.1016/j.imlet.2017.05.016DOI Listing
September 2017

The role of CR3 (CD11b/CD18) and CR4 (CD11c/CD18) in complement-mediated phagocytosis and podosome formation by human phagocytes.

Immunol Lett 2017 09 26;189:64-72. Epub 2017 May 26.

Department of Immunology, Eötvös Loránd University, Pázmány P. s. 1/C, Budapest H-1117, Hungary. Electronic address:

CR3 and CR4 belong to the family of β-integrins and play an important role in phagocytosis, cellular adherence and migration. CR3 and CR4 are generally expected to mediate similar functions due to their structural homology, overlapping ligand specificity and parallel expression on human phagocytes. Although the different signalling pathways of these receptors suggest distinct functions, possible differences are just being revealed. Previously we proved that CR3 plays a key role in the uptake of iC3b-opsonized particles by human dendritic cells. Now, besides measuring the overall phagocytic capacity of cells including the assessment of surface bound as well as internalized particles, we extended our investigations and studied the digestion of the iC3b opsonized antigen by various human phagocytes. The participation of CR3 and CR4 was compared in the process of binding, internalization and digestion of iC3b opsonized Staphylococcus aureus by monocytes, monocyte derived macrophages (MDMs), monocyte derived dendritic cells (MDDCs), and neutrophils. Comparing the activity of the two β-integrin type complement receptors we found that CR3 plays a dominant role in the phagocytosis of iC3b opsonized S. aureus by all of these cell types. Studying another important integrin-mediated function we demonstrated earlier that CR4 is dominant in the adhesion of monocytes, MDMs and MDDCs to fibrinogen. Here we studied the participation of CR3 and CR4 in podosome formation by human phagocytes, since these structures are known to play an essential role in cell migration. Our confocal microscopy analysis revealed that both CD11b and CD11c concentrate in the podosome adhesion ring. In summary our data highlight differences in the function of human CR3 and CR4 in the process of uptake and digestion of complement opsonized antigen, while in the process of podosome formation, connected to cellular motility, both receptors equally take part.
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http://dx.doi.org/10.1016/j.imlet.2017.05.014DOI Listing
September 2017

New opioid receptor antagonist: Naltrexone-14-O-sulfate synthesis and pharmacology.

Eur J Pharmacol 2017 Aug 11;809:111-121. Epub 2017 May 11.

Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4, P.O. Box 370, H-1445 Budapest, Hungary. Electronic address:

Opioid antagonists, naloxone and naltrexone have long been used in clinical practice and research. In addition to their low selectivity, they easily pass through the blood-brain barrier. Quaternization of the amine group in these molecules, (e.g. methylnaltrexone) results in negligible CNS penetration. In addition, zwitterionic compounds have been reported to have limited CNS access. The current study, for the first time gives report on the synthesis and the in vitro [competition binding, G-protein activation, isolated mouse vas deferens (MVD) and mouse colon assay] pharmacology of the zwitterionic compound, naltrexone-14-O-sulfate. Naltrexone, naloxone, and its 14-O-sulfate analogue were used as reference compounds. In competition binding assays, naltrexone-14-O-sulfate showed lower affinity for µ, δ or κ opioid receptor than the parent molecule, naltrexone. However, the μ/κ opioid receptor selectivity ratio significantly improved, indicating better selectivity. Similar tendency was observed for naloxone-14-O-sulfate when compared to naloxone. Naltrexone-14-O-sulfate failed to activate [S]GTPγS-binding but inhibit the activation evoked by opioid agonists (DAMGO, Iledeltorphin II and U69593), similarly to the reference compounds. Schild plot constructed in MVD revealed that naltrexone-14-O-sulfate acts as a competitive antagonist. In mouse colon, naltrexone-14-O-sulfate antagonized the inhibitory effect of morphine with lower affinity compared to naltrexone and higher affinity when compared to naloxone or naloxone-14-O-sulfate. In vivo (mouse tail-flick test), subcutaneously injected naltrexone-14-O-sulfate antagonized morphine's antinociception in a dose-dependent manner, indicating it's CNS penetration, which was unexpected from such zwitter ionic structure. Future studies are needed to evaluate it's pharmacokinetic profile.
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http://dx.doi.org/10.1016/j.ejphar.2017.05.024DOI Listing
August 2017

Opioid Receptor Activity and Analgesic Potency of DPDPE Peptide Analogues Containing a Xylene Bridge.

ACS Med Chem Lett 2017 Apr 14;8(4):449-454. Epub 2017 Mar 14.

Dipartimento di Farmacia, Università di Chieti-Pescara "G. d'Annunzio", Via dei Vestini 31, 66100 Chieti, Italy.

d-Pen,d-Pen enkephalin (DPDPE) is one of the most selective synthetic peptide agonists targeting the δ-opioid receptor. Three cyclic analogues of DPDPE containing a xylene bridge in place of disulfide bond have been synthesized and fully characterized as opioid receptors agonists. The activity was investigated showing a good affinity of - for μ- and δ-receptors. biological assays revealed that is the most potent analogue with the ability to maintain high level of analgesia from 15 to 60 min following intracerebroventricular (i.c.v.) administration, whereas DPDPE was slightly active until 45 min. Compound induced long lasting analgesia also after subcutaneous administration, whereas DPDPE was inactive.
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http://dx.doi.org/10.1021/acsmedchemlett.7b00044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5392763PMC
April 2017

Exploring the first Rimonabant analog-opioid peptide hybrid compound, as bivalent ligand for CB1 and opioid receptors.

J Enzyme Inhib Med Chem 2017 Dec;32(1):444-451

b Dipartimento di Chimica e Tecnologie del Farmaco , Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza Università di Roma , Roma , Italy.

Cannabinoid (CB) and opioid systems are both involved in analgesia, food intake, mood and behavior. Due to the co-localization of µ-opioid (MOR) and CB1 receptors in various regions of the central nervous system (CNS) and their ability to form heterodimers, bivalent ligands targeting to both these systems may be good candidates to investigate the existence of possible cross-talking or synergistic effects, also at sub-effective doses. In this work, we selected from a small series of new Rimonabant analogs one CB1R reverse agonist to be conjugated to the opioid fragment Tyr-D-Ala-Gly-Phe-NH. The bivalent compound (9) has been used for in vitro binding assays, for in vivo antinociception models and in vitro hypothalamic perfusion test, to evaluate the neurotransmitters release.
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http://dx.doi.org/10.1080/14756366.2016.1260565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6009935PMC
December 2017

Complement Receptor Type 1 Suppresses Human B Cell Functions in SLE Patients.

J Immunol Res 2016 17;2016:5758192. Epub 2016 Nov 17.

MTA-ELTE Immunology Research Group, Budapest, Eötvös Loránd University, Pázmány Péter s. 1/C, Budapest 1117, Hungary; Department of Immunology, Eötvös Loránd University, Pázmány Péter s. 1/C, Budapest 1117, Hungary.

Complement receptors (CRs) play an integral role in innate immunity and also function to initiate and shape the adaptive immune response. Our earlier results showed that complement receptor type 1 (CR1, CD35) is a potent inhibitor of the B cell receptor- (BCR-) induced functions of human B lymphocytes. Here we show that this inhibition occurs already at the initial steps of B cell activation since ligation of CR1 reduces the BCR-induced phosphorylation of key signaling molecules such as Syk and mitogen activated protein kinases (MAPKs). Furthermore, our data give evidence that although B lymphocytes of active systemic lupus erythematosus (SLE) patients express lower level of CR1, the inhibitory capacity of this complement receptor is still maintained and its ligand-induced clustering results in significant inhibition of the main B cell functions, similar to that found in the case of healthy individuals. Since we have found that reduced CR1 expression of SLE patients does not affect the inhibitory capacity of the receptor, our results further support the therapeutical potential of CD35 targeting the decrease of B cell activation and autoantibody production in autoimmune patients.
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http://dx.doi.org/10.1155/2016/5758192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5131247PMC
March 2017

The versatile functions of complement C3-derived ligands.

Immunol Rev 2016 11;274(1):127-140

Department of Immunology, Eötvös Loránd University, Budapest, Hungary.

The complement system is a major component of immune defense. Activation of the complement cascade by foreign substances and altered self-structures may lead to the elimination of the activating agent, and during the enzymatic cascade, several biologically active fragments are generated. Most immune regulatory effects of complement are mediated by the activation products of C3, the central component. The indispensable role of C3 in opsonic phagocytosis as well as in the regulation of humoral immune response is known for long, while the involvement of complement in T-cell biology have been revealed in the past few years. In this review, we discuss the immune modulatory functions of C3-derived fragments focusing on their role in processes which have not been summarized so far. The importance of locally synthesized complement will receive special emphasis, as several immunological processes take place in tissues, where hepatocyte-derived complement components might not be available at high concentrations. We also aim to call the attention to important differences between human and mouse systems regarding C3-mediated processes.
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http://dx.doi.org/10.1111/imr.12498DOI Listing
November 2016

CD11c/CD18 Dominates Adhesion of Human Monocytes, Macrophages and Dendritic Cells over CD11b/CD18.

PLoS One 2016;11(9):e0163120. Epub 2016 Sep 22.

Department of Immunology, Institute of Biology, Faculty of Science, Eötvös Loránd University, Budapest, Hungary.

Complement receptors CR3 (CD11b/CD18) and CR4 (CD11c/CD18) belong to the family of beta2 integrins and are expressed mainly by myeloid cell types in humans. Previously, we proved that CR3 rather than CR4 plays a key role in phagocytosis. Here we analysed how CD11b and CD11c participate in cell adhesion to fibrinogen, a common ligand of CR3 and CR4, employing human monocytes, monocyte-derived macrophages (MDMs) and monocyte-derived dendritic cells (MDDCs) highly expressing CD11b as well as CD11c. We determined the exact numbers of CD11b and CD11c on these cell types by a bead-based technique, and found that the ratio of CD11b/CD11c is 1.2 for MDDCs, 1.7 for MDMs and 7.1 for monocytes, suggesting that the function of CD11c is preponderant in MDDCs and less pronounced in monocytes. Applying state-of-the-art biophysical techniques, we proved that cellular adherence to fibrinogen is dominated by CD11c. Furthermore, we found that blocking CD11b significantly enhances the attachment of MDDCs and MDMs to fibrinogen, demonstrating a competition between CD11b and CD11c for this ligand. On the basis of the cell surface receptor numbers and the measured adhesion strength we set up a model, which explains the different behavior of the three cell types.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5033469PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0163120PLOS
September 2016
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