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T cell lysis of murine renal cancer: multiple signaling pathways for cell death via Fas
Author(s) -
Sayers Thomas J.,
Brooks Alan D.,
Seki Naoko,
Smyth Mark J.,
Yagita Hideo,
Blazar Bruce R.,
Malyguine Anatoli M.
Publication year - 2000
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.68.1.81
Subject(s) - fas ligand , lysis , biology , apoptosis , reactive oxygen species , microbiology and biotechnology , programmed cell death , cancer research , biochemistry
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.