Effects of murine tumor necrosis factor on Friend erythroleukemic cells.
Tumor necrosis inducing factor (TNF), a 140,000 molecular weight glycoprotein present in the serum of Corynebacterium parvum endotoxin-treated mice, was cytotoxic toward Friend virus-transformed erythroleukemic cells (FELC). These cells grow in culture as undifferentiated pro-erythroblasts but can be induced to differentiate in a limited fashion along the erythroid pathway to orthochromatic normoblasts by various agents such as dimethylsulfoxide (DMSO). Partially and highly purified preparations of TNF were cytotoxic toward logarithmically growing FELC whereas a comparable serum protein fraction from C. parvum treated mice or endotoxin from E. coli had no effect upon FELC viability. DMSO-induced cells were more sensitive to the action of TNF requiring only about half the concentration needed to produce 50% kill in noninduced cells. Inhibition of hemoglobin formation was TNF dose-related and could be decreased by 94%. TNF was also cytotoxic toward DMSO-induced cells in stationary phase and mitomycin C treated noninduced FELC. Neuraminidase modification of the surface of FELC increased the cytotoxicity of TNF by 50%. These results demonstrate that TNF destroys FELC whether they are nondividing, dividing or partially differentiated and suggest that TNF may accomplish this by affecting cell metabolism after internalization.
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006023:Glycoproteins / Q000633:toxicity*; D006131:Growth Inhibitors / Q000633:toxicity*; D004915:Leukemia, Erythroblastic, Acute / Q000628:therapy; D007942:Leukemia, Experimental / Q000628:therapy*; D051379:Mice; D009439:Neuraminidase; D014409:Tumor Necrosis Factor-alpha
D006023:Glycoproteins; D006131:Growth Inhibitors; D014409:Tumor Necrosis Factor-alpha; D009439:Neuraminidase; D004121:Dimethyl Sulfoxide