Role of fas and bcl-2 in sensitivity of target to macrophage mediated cytotoxicity

A. A. Pimenov, E. R. Podack

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The role of apoptosis as a mechanism for macrophage (Mo)mediated tumor cytotoxicity is unclear. We tested the presence of Fas-based mechanisms of Mo cytotoxicity in several experimental models: (1) comparison of the sensitivity to activated Mo of different tumor cell lines before and after transfection with Fas or bcl-2, (2) search for differences in cytotoxicity of Mo from Fas-ligand (FasL) sufficient and FasL deficient (gld) mutant mice, (3) quantitation of FasL mRNA expression in Mo by PCR. P815 tumor cells transfected with Fas is much more sensitive to Mo than untransfected P815 or transfected with TNFRI or vector only. P815 transfected with bcl-2, which is known to protect against apoptosis, are killed significantly less than untransfected P815 by Mo. Mo cytotoxicity against P815 and P815-Fas was completely prevented by a specific inhibitor of nitric oxide synthase, N-MMA. On the contrary, anti-TNF antibody or Fas-lg fusion protein were ineffective inhibitors of cytotoxicity. Mo from C3H/J and C3H/gld are equally effective in killing of P815 or P815-fas. There is no difference in sensitivity of Mo resistant tumor cell lines: EL-4 and L1210 before and after Fas transfection. Finally we have not found detectable levels of FasL mRNA expression in activated Mo. Supported by grant from NIH and CCORFDP award.

Original languageEnglish (US)
Pages (from-to)A1340
JournalFASEB Journal
Issue number6
StatePublished - Dec 1 1996

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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