Kupffer Cells and Peritoneal Macrophage Activation After Platinum Coordination Complexes

Action of poly-[(trans-l,2-diaminocyclohexane)platinum]-carboxyamylose (poly-plat) and cisplatin (CDDP) on the immune system was studied using isolated peritoneal macrophages and compared with liver resident macrophages from normal, CDDP and poly-plat [10 mg/kg] treated Swiss Webster mice for 2-12 days. Peritoneal macrophages were treated [10 mg/L] for 2 h and allowed to grow in normal medium at 37C (5% CO2) for 24 h. Similarly macrophages from Swiss Webster mice treated with CDDP and poly-plat were isolated and cultured on normal medium. Supernatants from cells in culture were collected at 0.5, 1, 2, and 24 h post-treatment for various cytolytic factors. CDDP and poly-plat treatments induce an activation of the peritoneal macrophages and the Kupffer cells through cell growth, development of cytoplasmic extensions, enhanced number of lysosomes and the activity of various cytolytic factors. Poly-plat treatment of the macrophages induces a 500 fold increase in the number of lysosomes, compared to CDDP treatment where there was only a 50 fold increase.