Lymphocytes with cytotoxic activity induce rapid microtubule axonal destabilization independently and before signs of neuronal death.

Authors:
Nichole M Miller
Nichole M Miller
Blood Research Institute
United States
Leah P Shriver
Leah P Shriver
Blood Research Institute
United States
Vijaya L Bodiga
Vijaya L Bodiga
Blood Research Institute
United States
Avijit Ray, PhD
Avijit Ray, PhD
AbbVie
Senior Scientist II
Immunology, Immuno-oncology, Autoimmunity and Inflammation, Immune tolerance
North Chicago, IL | United States
Sreemanti Basu
Sreemanti Basu
Blood Research Institute
United States
Rajiv Ahuja
Rajiv Ahuja
University of Tennessee
United States
Arundhati Jana
Arundhati Jana
Rush University Medical Center
United States
Kalipada Pahan
Kalipada Pahan
Rush University Medical Center
Chicago | United States

ASN Neuro 2013 Feb 6;5(1):e00105. Epub 2013 Feb 6.

BloodCenter of Wisconsin, Blood Research Institute, Milwaukee, WI 53226, USA.

MS (multiple sclerosis) is the most prevalent autoimmune disease of the CNS (central nervous system) historically characterized as an inflammatory and demyelinating disease. More recently, extensive neuronal pathology has lead to its classification as a neurodegenerative disease as well. While the immune system initiates the autoimmune response it remains unclear how it orchestrates neuronal damage. In our previous studies, using in vitro cultured embryonic neurons, we demonstrated that MBP (myelin basic protein)-specific encephalitogenic CD4 T-cells induce early neuronal damage. In an extension of those studies, here we show that polarized CD4 Th1 and Th17 cells as wells as CD8 T-cells and NK (natural killer) cells induce microtubule destabilization within neurites in a contact-independent manner. Owing to the cytotoxic potential of these immune cells, we isolated the luminal components of lytic granules and determined that they were sufficient to drive microtubule destabilization. Since lytic granules contain cytolytic proteins, we determined that the induction of microtubule destabilization occurred prior to signs of apoptosis. Furthermore, we determined that microtubule destabilization was largely restricted to axons, sparing dendrites. This study demonstrated that lymphocytes with cytolytic activity have the capacity to directly drive MAD (microtubule axonal destabilization) in a bystander manner that is independent of neuronal death.

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http://dx.doi.org/10.1042/AN20120087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3565378PMC

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February 2013
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References

(Supplied by CrossRef)
Article in J Immunol
Awane M et al.
J Immunol 1999

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