CISPLATIN STIMULATES PROTEIN-TYROSINE PHOSPHORYLATION IN MACROPHAGES

Cisplatin [cis-dichlorodiamine platinum (II)], a potent anti-tumor com pound, stimulates immune responses by activating monocyte-macrophages and other cells of the immune system. The mechanism by which cisplatin activates these cells is poorly characterized. Since protein tyrosine phosphorylation appears to be a major intracellular signalling event that mediates cellular responses, we examined whether cisplatin alters tyrosine phosphorylation in macrophages. We found that cisplatin incr eased tyrosine phosphorylation of several proteins in peritoneal macro phages and in P388D1 and IC-21 macrophage cell lines. Treatment of mac rophages with tyrosine kinase inhibitors, genestein and lavendustin A, inhibited cisplatin-stimulated protein tyrosine phosphorylation in ma crophages. Macrophages treated with cisplatin also exhibit increased f luorescence with anti-phosphotyrosine-FITC antibody. These data indica te that protein tyrosine phosphorylation plays a role in cisplatin-ind uced activation of macrophages.