Bcl-2 blocks degranulation but not fas-based cell-mediated cytotoxicity.
The ability of bcl-2 in target cells to block cell-mediated cytotoxicity by allospecific CTL was tested. The blocking effect was variable. Because killing by CTL involves two different pathways, degranulation (perforin plus granzymes) and fas, we examined the effect of bcl-2 on these pathways independently. Bcl-2 in target cells blocked apoptotic cell death induced either by cytotoxic granule extracts or by CTL killing under conditions in which the fas pathway is blocked. On the other hand, bcl-2 had no effect on target cell-killing either by Fas-specific mAb or by CTL capable of killing only via the fas pathway. These data suggest bcl-2 may block apoptotic lysis induced by perforin plus granzymes, but not apoptotic lysis induced via the fas pathway. Thus, any analysis of the effect of bcl-2 on apoptotic cell death in target cells killed by CTL must take into account the relative contributions of the degranulation vs fas pathways.
Chiu
V K
VK
Department of Biology and Molecular Biology Institute, University of California at Los Angeles 90024.
Walsh
C M
CM
Liu
C C
CC
Reed
J C
JC
Clark
W R
WR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000954:Antigens, Surface / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D015550:Cell Degranulation / Q000235:genetics* / Q000276:immunology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000235:genetics*; D003907:Dexamethasone / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics; D051379:Mice; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D019014:fas Receptor
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D003907:Dexamethasone