EXPRESSION OF LFA-1 ADHESION MOLECULES ON CISPLATIN-TREATED MACROPHAGES

Appropriately activated mononuclear phagocytes mediate contact-depende nt tumoricidal activity. Adhesion structures involved in contact-depen dent tumor cytotoxicity have not been defined. The present study was a imed at identifying the adhesion structure involved in the tumoricidal activity of cisplatin-activated murine peritoneal macrophages. Tumor cells of different histological origin were used as targets in a 24-h cytotoxicity assay. Anti-CD18 (LFA-1 beta) substantially inhibited mac rophage cytotoxicity whereas anti-LFA-1 alpha marginally inhibited mac rophage-mediated cytotoxicity. When combined together, almost complete inhibition of tumoricidal activity was observed. Activated macrophage s showed augmented binding to target cells and anti-LFA MAb inhibited the binding of resting,a and activated macrophages to target cells. Ci splatin augmented the expression of LFA-1 alpha and beta integrins and LPS had no effect as assessed by immunoprecipitation. These results i mplicate that in cisplatin activated macrophages LFA-1 alpha and beta integrins are important molecules in contact-dependent tumoricidal act ivity. (C) 1998 Elsevier Science B.V.