INTERLEUKIN-10 DECREASES TYROSINE PHOSPHORYLATION OF DISCRETE LIPOPOLYSACCHARIDE-INDUCED PHOSPHOPROTEINS IN HUMAN GRANULOCYTES

Although Interleukin-10 (IL-10) has been recently shown to modulate li popolysaccharide (LPS)-induced release of cytokines in human granulocy tes, the intracellular signalling pathways of LPS have been only parti ally defined, while those of IL-10 remain unknown. The present study s hows that LPS induces an increase in tyrosine phosphorylation of a dis crete number of proteins, in a time- and concentration-dependent manne r. Tn addition, IL-10 negatively influenced protein tyrosine phosphory lation in LPS-treated human polymorphonuclear leukocytes (PMN). The ef fect of IL-10 was evident only after 60 min LPS-stimulation and was de tected by analysing either cell lysates or lysates which were previous ly immunoprecipitated with anti-phosphotyrosine antibodies. Amongst th e tyrosine phosphoproteins mostly affected by IL-10 in LPS-stimulated cells were the species with molecular weights ranging from 46 to 49 kD a. The identity and possible function of these proteins remain unknown . Taken together, our results suggest that tyrosine phosphorylation ma y constitute one of the intracellular events that mediate LPS and IL-1 0 responses in granulocytes. (C) 1995 Academic Press, Inc.