Tumour-necrosis factor from the rabbit. I. Mode of action, specificity and physicochemical properties.
Sera from rabbits injected with BCG and then with endotoxin contain a factor (tumour-necrosis factor TNF) which, even at high dilutions, is cytotoxic in vitro for mouse L cells and some other cell lines. Using a 51Cr-release assay, cytotoxicity was detected as early as 7-8 h after addition of TNF serum to L cells and cell death was evident microscopically by 24 h. TNF was cytotoxic at 37 degrees C but not at 21 degrees C or 4 degrees C, and acted on both dividing and non-dividing cells. The antimetabolites sodium azide and dinitrophenol partially protected L cells from TNF, suggesting that actively metabolizing cells are the most sensitive. Treatment of L cells with trypsin did not delay cytotoxicity nor was cytotoxicity inhibited in the presence of various saccharide derivatives of cell-surface glycoproteins. Rabbit TNF was remarkably stable with a mol. wt. of 40-50,000. It was eluted with the more acidic serum proteins on ion-exchange chromatography, but precipitated in 50%-saturated ammonium sulphate. Sensitivity to TNF could not be correlated with tumourigenicity of several animal and human lines tested nor with the production of C-type viruses.
D000818:Animals; D001386:Azides / Q000494:pharmacology; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004140:Dinitrophenols / Q000494:pharmacology; D006023:Glycoproteins; D007739:L Cells / Q000276:immunology; D009005:Monosaccharides / Q000494:pharmacology; D009374:Neoplasms, Experimental / Q000276:immunology*; D011134:Polysaccharides / Q000494:pharmacology; D011817:Rabbits; D013696:Temperature; D013997:Time Factors; D014357:Trypsin / Q000494:pharmacology
D001386:Azides; D004140:Dinitrophenols; D006023:Glycoproteins; D009005:Monosaccharides; D011134:Polysaccharides; D014357:Trypsin