T cell lysis of murine renal cancer: multiple signaling pathways for cell death via Fas.
Activated T cells lyse the murine renal cancer Renca. We have examined the mechanism of tumor cell lysis with the use of T cells derived from C57BL/6, BALB/c, B6.gld, and B6.Pfp-/- mice. C57BL/6 and BALB/c T cells can lyse Renca cells through the use of both granule- and Fas ligand (FasL)-mediated pathways. However, B6.gld T cells predominantly use granule-mediated killing, whereas B6.Pfp-/- T cells use FasL. The lysis of Renca by Pfp-/- T cells is only partially inhibited by the caspase inhibitor ZVAD-FMK, suggesting that caspase-independent signaling is also important for Renca cell lysis. When the reactive oxygen scavenger butylated hydroxyanisole was used alone or in combination with ZVAD-FMK a substantial reduction of Renca lysis was observed. Therefore, the caspase-independent generation of reactive oxygen intermediates in Renca after Fas triggering contributes to the lysis of these cells.
Intramural Research Support Program, SAIC-Frederick, DBS, NCI-FCRDC, Maryland 21702-1201, USA. Sayers@mail.ncifcrf.gov
T J
TJ
Sayers
A D
AD
Brooks
N
N
Seki
M J
MJ
Smyth
H
H
Yagita
B R
BR
Blazar
A M
AM
Malyguine
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000473:pathology; D020169:Caspases / Q000502:physiology; D003433:Crosses, Genetic; D003594:Cytoplasmic Granules / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D004151:Dipeptides / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053222:Fas Ligand Protein; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007659:Ketones / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D013047:Specific Pathogen-Free Organisms; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014162:Transfection; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D019014:fas Receptor / Q000235:genetics / Q000502:physiology*
D000590:Amino Acid Chloromethyl Ketones; D051017:Apoptosis Regulatory Proteins; D004151:Dipeptides; D004791:Enzyme Inhibitors; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D016166:Free Radical Scavengers; D007659:Ketones; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D019014:fas Receptor; C057383:MDL 201053; D002083:Butylated Hydroxyanisole; D007371:Interferon-gamma; D020169:Caspases