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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.
Insights
Tumor necrosis factor (TNF) is a serum glycoprotein that effectively kills Friend virus-transformed erythroleukemic cells (FELC). Its cytotoxic effect is enhanced in partially differentiated or surface-modified FELC, suggesting potential therapeutic applications.
Area of Science:
- Immunology
- Cell Biology
- Cancer Research
Background:
- Tumor necrosis factor (TNF) is a glycoprotein found in the serum of mice treated with Corynebacterium parvum endotoxin.
- Friend virus-transformed erythroleukemic cells (FELC) are undifferentiated pro-erythroblasts that can be induced to differentiate.
Purpose of the Study:
- To investigate the cytotoxic effects of TNF on FELC.
- To determine factors influencing TNF-mediated cytotoxicity.
- To explore the potential mechanisms of TNF action on FELC.
Main Methods:
- Preparation of partially and highly purified TNF.
- Treatment of FELC with TNF under various conditions (logarithmic growth, DMSO-induced differentiation, stationary phase, mitomycin C treatment).
- Modification of FELC surface with neuraminidase.
- Assessment of FELC viability and hemoglobin formation.
Main Results:
- Purified TNF demonstrated significant cytotoxicity against logarithmically growing FELC.
- DMSO-induced FELC were more sensitive to TNF, requiring half the concentration for 50% cell kill.
- TNF inhibited hemoglobin formation in a dose-dependent manner.
- TNF exhibited cytotoxicity against non-dividing, dividing, and partially differentiated FELC.
- Neuraminidase treatment of FELC increased TNF cytotoxicity by 50%.
Conclusions:
- TNF is cytotoxic to FELC across different cellular states, including differentiated and non-dividing cells.
- TNF's mechanism may involve internalization and subsequent effects on cell metabolism.
- These findings suggest TNF's potential role in targeting erythroleukemic cells.