Mechanisms of TNF resistance: identification of membrane phosphoproteins associated with a dominant resistant phenotype in lymphoid-myeloid somatic cell hybrids.
Analysis of 53 somatic cell hybrids between TNF-sensitive myeloid cells (U937) and TNF-resistant T-cell lines HUT78 (UH-hybrids) and Jurkat (UJ-hybrids), respectively, revealed complete resistance to TNF-mediated cytostasis in all cases. Moreover, all hybrids remained insensitive to a combined treatment with TNF-alpha and IFN-gamma, which exert synergistic growth inhibition and cytotoxicity on parental U937 cells. Analyses of cell surface marker expression, membrane phosphoproteins, and expression of tissue-specific cytokine genes revealed differential conservation of myeloid and T-cell-specific properties in each of these hybrids, but invariant, dominant resistance to TNF-alpha-mediated growth inhibition. All TNF-resistant hybrids expressed a membrane phosphoprotein pattern, which closely resembled that of the respective parental T-cell lines. In particular, two membrane phosphoproteins of apparent molecular weight of 50,000 and 38,000 were common in the two parental T-cell lines and all UH- and UJ-hybrid clones, suggesting a possible role of these proteins in mediating TNF resistance.
Schütze
S
S
Clinical Research Group, Max-Planck-Society, University of Göttingen, FRG.
Nottrott
S
S
Scheurich
P
P
Krönke
M
M
Pfizenmaier
K
K
D000954:Antigens, Surface / Q000276:immunology; D002459:Cell Fusion; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D005799:Genes, Dominant; D006801:Humans; D006822:Hybrid Cells / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics*; D007951:Leukemia, Myeloid / Q000235:genetics*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D010641:Phenotype; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics*; D012313:RNA / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics*
D000954:Antigens, Surface; D008565:Membrane Proteins; D010750:Phosphoproteins; D014409:Tumor Necrosis Factor-alpha; D012313:RNA; D007371:Interferon-gamma