MHC class II-mediated apoptosis in dendritic cells: a role for membrane-associated and mitochondrial signaling pathways
| Autor: | Alexander D. McLellan, Martina Heldmann, Eva-B. Bröcker, Eckhart Kämpgen, Martin Leverkus, Norbert Koch, Andreas O. Eggert |
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| Rok vydání: | 2003 |
| Předmět: |
Time Factors
Apoptosis Amino Acid Chloromethyl Ketones Membrane Potentials Jurkat Cells Mice Immunology and Allergy Cytotoxic T cell Annexin A5 Enzyme Inhibitors Caspase Cell Aggregation Mice Knockout Mice Inbred BALB C biology Cell Death Antibodies Monoclonal Cell Differentiation General Medicine Flow Cytometry Caspase Inhibitors Cell biology Transport protein Mitochondria Proto-Oncogene Proteins c-bcl-2 Caspases Signal transduction Signal Transduction Programmed cell death Immunology Bone Marrow Cells Mice Inbred Strains Mice Transgenic Dinoprostone Animals Humans CD40 Antigens MHC class II Interleukins Histocompatibility Antigens Class II Granulocyte-Macrophage Colony-Stimulating Factor Dendritic cell Dendritic Cells Molecular biology Mice Inbred C57BL Microscopy Electron biology.protein Interleukin-4 Cell Adhesion Molecules |
| Zdroj: | International immunology. 15(8) |
| ISSN: | 0953-8178 |
| Popis: | Cytotoxic elimination of dendritic cells (DC) in lymphoid tissue represents an important pathway of immune regulation. However, the mechanism of DC removal is still controversial since mature DC are insensitive to death receptor-mediated killing and other surface or soluble molecules mediating DC death in vivo have yet to be characterized. Class II ligation is the only known signal that induces rapid cell death in mature DC, thus our studies have now focused on the requirements for this cell death using the advantages of tools available for both the mouse and human systems. Anti-class II mAb could be grouped into (i) mAb that both bound to class II and caused class II-mediated cell death as well as (ii) those that bound to class II, but did not cause apoptosis. mAb binding stable class II dimers as well as those mAb recognizing either the alpha or beta chains of class II were found in both groups. Whereas class II-mediated death was enhanced by DC-DC homotypic interactions, DC clustering itself was insufficient to induce apoptosis. Although DC death could be inhibited by uncoupling actin filament bundling, the inhibition of various proteases, including the caspases, and protein transport mediators failed to inhibit class II-mediated cell death. Neither Bid, poly-ADP-ribose polymerase, caspases-3, -7 and -8 nor FLICE-inhibitory protein were found to be cleaved during class II apoptosis. Lastly, although class II mAb induced a rapid mitochondrial membrane depolarization in DC, cell death was not inhibited by Bcl-2 over-expression in DC. The independence of this form of apoptosis from protein or RNA synthesis, coupled to the rapidity of the mitochondrial depolarization and the lack of protection by Bcl-2, suggests that mature DC express pre-formed pro-apoptotic molecules that are involved in class II-mediated death. |
| Databáze: | OpenAIRE |
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