ENDOTOXIN-INDUCED PROTEIN-PHOSPHORYLATION IN MACROPHAGES IS MODULATEDBY TUMOR-CELLS

Tumor cells are known to modulate the antitumor functions of endotoxin or cytokine-stimulated macrophages, however, their mechanism of actio n is not known. We have recently shown that Dalton's lymphoma (DL, a m urine 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 PK C from cytosol to the membrane fraction. Incubation of macrophages wit h DL cells or DL cell lysate (DLL) resulted in a significant decrease in the PKC activity in membrane fraction compared to the LPS-treated m acrophages 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 w ere found to increase the protein tyrosine phosphorylation whereas DLL did not have any effect on protein tyrosine phosphorylation in macrop hages. These results thus suggest that tumor cells and/or their produc ts can differentially effect the phosphorylation of different proteins involved in cell signalling. (C) 1998 International Society for Immun opharmacology. Published by Elsevier Science Ltd. All rights reserved.