Endotoxin-induced protein phosphorylation in macrophages is modulated by tumor cells.
Tumor cells are known to modulate the antitumor functions of endotoxin or cytokine-stimulated macrophages, however, their mechanism of action is not known. We have recently shown that Dalton's lymphoma (DL, a murine spontaneous T cell lymphoma) alter the activation of macrophages by lipopolysaccharide (LPS). In this investigation, the effects of DL cells on protein kinase C (PKC) activity, calcium uptake and protein tyrosine phosphorylation in murine peritoneal macrophages was studied. Treatment of macrophages with LPS resulted in the translocation of PKC from cytosol to the membrane fraction. Incubation of macrophages with DL cells or DL cell lysate (DLL) resulted in a significant decrease in the PKC activity in membrane fraction compared to the LPS-treated macrophages incubated without DL cells or DLL. DL cells were also found to inhibit the accumulation and influx of calcium in the macrophages in response to LPS. On the other hand, DL cells augmented the protein tyrosine phosphorylation in murine macrophages. Only viable DL cells were found to increase the protein tyrosine phosphorylation whereas DLL did not have any effect on protein tyrosine phosphorylation in macrophages. These results thus suggest that tumor cells and/or their products can differentially effect the phosphorylation of different proteins involved in cell signalling.
Department of Zoology, University of Delhi, India.
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Kumar
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Singh
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Sodhi
D000818:Animals; D002118:Calcium / Q000493:pharmacokinetics; D002450:Cell Communication / Q000502:physiology; D002462:Cell Membrane / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016399:Lymphoma, T-Cell / Q000473:pathology*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D008070:Lipopolysaccharides; D011506:Proteins; D014443:Tyrosine; D011493:Protein Kinase C; D002118:Calcium