P. Vandenabeele et al., FUNCTIONAL REQUIREMENT OF THE 2 TNF RECEPTORS FOR INDUCTION OF APOPTOSIS IN PC60 CELLS AND THE ROLE OF MITOCHONDRIA IN TNF-INDUCED CYTOTOXICITY, Circulatory shock, 44(4), 1994, pp. 196-200
The rat/mouse T-cell hybridoma PC60 was transfected either with hTNF-R
55 cDNA, hTNF-R75 cDNA, or both. Receptor-specific stimulation was ach
ieved using agonistic monoclonal antibodies or receptor-specific mutei
ns of hTNF. Either hTNF-R55 or hTNF-R75 could mediate the activation o
f NF-kappa B and the induction of GM-CSF, IL-6, and IFN-gamma. But onl
y in cells carrying both hTNF-R55 and hTNF-R75, was TNF able to induce
apoptosis. This apoptosis could be inhibited almost completely by cot
ransfection with human bcl-2 cDNA. Functional cooperation was observed
between liganded and unliganded receptors for the induction of apopto
sis. in vitro protein kinase activity was detected only in TNF-R75 imm
unoprecipitates from cells in which the receptor was signaling. Direct
evidence was obtained for reactive oxygen intermediates of mitochondr
ial origin responsible for TNF-induced cytotoxicity in L929 cells. (C)
1995 Wiley-Liss, Inc.