Effects of Murine Tumor Necrosis Factor on Friend Erythroleukemic Cells

Abstract

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.

Antitumor Activity of Normal Human Globulin: Effects on Murine and Human Erythroleukemic Cells

“…In contrast. TNF under identical conditions produced the same results following 4-hour exposure that was obtained only after 12 h of incubation with NHG-I [15].…”

“…Koo [9] has character ized the growth inhibitory activity associated with an a 2-macroglobulin fraction from mice and lately [10] described a cytotoxic effect upon various human and murine tumor cell lines of a human < X 2-macroglobulin. We have recently studied the effect of TNF upon erythroleukemic cells [13,15] and here report the results of similar studies using NHG-I.…”

Measurement of tumor necrosis factor activity by flow cytometry

“…Cells of the mononuclear phagocyte lineages are the primary source of TNF-a, but it is now known that many other cell types produce this cytokine, including lymphocytes, mast cells, and even fibroblasts ( 15). TNF is involved in various pathological and physiological situations, and it is implicated alone or in association with other cytokines such as interleukin (1L)-I , IL-6, and interferons in the pathogenesis of different diseases such as septic shock and cerebral malaria and autoimmune diseases such as rheumatoid arthritis (17,10,7).Various assays have been reported for the measurement of TNF cytotoxicity (1,3,5,8,9,(11)(12)(13)16 Recombinant TNF The recombinant human TNF-a used for these assays was produced in our laboratory (14). This purified TNF-a had a specific activity of 10' units per milligram as determined by the standard T N F assay of Aggarwal and Kohr ( 1 ).…”

“…Various assays have been reported for the measurement of TNF cytotoxicity (1,3,5,8,9,(11)(12)(13)16 Recombinant TNF The recombinant human TNF-a used for these assays was produced in our laboratory (14). This purified TNF-a had a specific activity of 10' units per milligram as determined by the standard T N F assay of Aggarwal and Kohr ( 1 ).…”

Suppression of Friend Virus-induced Leukaemia in Mice by Tuftsin

“…We have recently shown that tuftsin stimulates the production of tumour necrosis factor (TNF) (Wleklik et al, 1985), which is known to be responsible for the necrosis of various tumours (Maranaska et al, 1984). This may be of special interest as Suyama et al (1985) have shown that TNF is cytotoxic towards FLV-transformed erythroleukaemic cells.…”