Lymphocytes with Cytotoxic Activity Induce Rapid Microtubule Axonal Destabilization Independently and before Signs of Neuronal Death
| Autor: | Vijaya L. Bodiga, Kalipada Pahan, Leah P. Shriver, Nichole M. Miller, Arundhati Jana, Avijit Ray, Bonnie N. Dittel, Rajiv Ahuja, Sreemanti Basu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
CD4-Positive T-Lymphocytes
MBP myelin basic protein NK cells multiple sclerosis Microtubules Granzymes Mice MAD microtubule axonal destabilization MEM minimal essential medium 0302 clinical medicine TGFβ transforming growth factor β Demyelinating disease Lymphocytes BBB blood–brain barrier Cells Cultured EAE experimental autoimmune encephalomyelitis Neurons Microscopy Confocal Cell Death biology General Neuroscience APC antigen presenting cells Neurodegeneration CD8 T-cell neurodegeneration axonopathies 3. Good health Cell biology Killer Cells Natural CD4 T-cell FBS foetal bovine serum Cytokines NK natural killer Research Article Programmed cell death Encephalomyelitis Autoimmune Experimental Neurite IFNγ interferon γ S6 MAP2 microtubule associated protein Mice Transgenic S3 CNS central nervous system Models Biological MS multiple sclerosis lcsh:RC321-571 OVA ovalbumin 03 medical and health sciences Bacterial Proteins CA conalbumin Microtubule In Situ Nick-End Labeling medicine Animals lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Perforin Myelin Basic Protein Th1 Cells Embryo Mammalian medicine.disease YFP yellow fluorescent protein Axons IL interleukin Myelin basic protein Mice Inbred C57BL Luminescent Proteins TUNEL terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling Granzyme TCR T-cell receptor Culture Media Conditioned biology.protein Th17 Cells Neurology (clinical) PFA paraformaldehyde 030217 neurology & neurosurgery DAPI 4′ 6-diamidino-2-phenylindole 030215 immunology |
| Zdroj: | ASN Neuro, Vol 5 (2013) ASN NEURO |
| ISSN: | 1759-9091 1759-0914 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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