Antigen presentation by cisplatin-activated macrophages: role of soluble factor(s) and second messengers

Cisplatin [cis-dichlorodiammine platinum (II)], a potent anti-tumour compound, stimulates immune responses by activating macrophages and other cells of the immune system. The mechanism by which cisplatin activates these cells is poorly characterized. Present investigations were undertaken to study the mechanism of antigen presentation by cisplatin-treated macrophages. Cisplatin-treated macrophages showed a biphasic pattern of antigen presentation to keyhole limpet haemocyanin (KLH)-primed T cells. The second phase of antigen presentation was not due to the continuous presence of cisplatin in the culture medium; rather, it was induced by soluble factors released by cisplatin-treated macrophages. Co-incubation of macrophages with cisplatin and inhibitor of serine/threonine or protein tyrosine phosphatase resulted in an augmentation of cisplatin-induced antigen presentation. In contrast, treatment of macrophages with cisplatin and inhibitor of protein kinase C or protein tyrosine kinase inhibited cisplatin-induced antigen presentation. These observations suggest that antigen presentation by cisplatin-treated macrophages is regulated by reversible action of protein phosphatases and kinases. The antigen-presenting ability of cisplatin-treated macrophages was also inhibited by EGTA, nifedipine, TMB-8, W-7 and calmidazolium, suggesting the probable involvement of Ca2+, calmodulin and calmodulin-dependent kinases in this process.