Both tumor necrosis factor and nitric oxide participate in lysis of simian virus 40-transformed cells by activated macrophages.
SV40 transformation of rodent fibroblasts generally produces cells that are highly sensitive to killing by activated macrophages. The cell line SV-COL-E8 (E8) is typical of SV40-transformed mouse fibroblasts in that it is readily lysed when exposed to activated macrophages. This killing is not due solely to TNF, because soluble TNF alone is incapable of lysing these cells. TNF is, however, necessary for lysis since antibodies to TNF will prevent macrophage-mediated lysis. Similarly, E8 is not sensitive to nitric oxide (NO); however, NO is also necessary for lysis since inhibition of NO generation (by coincubation with the arginine analogue NG-monomethyl-1-arginine) with Fe(II)) blocks lysis of E8 by activated macrophages. Cytolysis by macrophages is contact dependent, suggesting that the cell-associated TNF precursor may be involved in mediating cytolysis. However, transfected cell lines bearing cell-associated TNF precursor do not mediate killing of E8. Thus, killing of E8 either involves both TNF and NO in addition to a third, as yet unidentified, lytic mechanism, or killing requires the contact-dependent delivery of TNF and NO from the macrophage to its target.
Duerksen-Hughes
P J
PJ
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322.
Day
D B
DB
Laster
S M
SM
Zachariades
N A
NA
Aquino
L
L
Gooding
L R
LR
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D007501:Iron / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D009569:Nitric Oxide / Q000633:toxicity*; D013539:Simian virus 40; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*; D019323:omega-N-Methylarginine
D014409:Tumor Necrosis Factor-alpha; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D007501:Iron