1998 年 24 巻 1 号 p. 1-12
In this study we report that the activation of murine bone marrow-derived macrophages (BMDM) to the tumoricidal state by cisplatin is a Ca2+- and calmodulin-dependent process. Cisplatin induced an increase in [Ca2+]i in fura-2/AM-loaded BMDM in a cisplatin concentration-dependent manner, as evidenced by progressive increase in the relative fluorescence of the treated cells. Cisplatin-treated BMDM also showed a gradual increase in their ATP level in a cisplatin concentrationdependent manner. There was marked down-regulation of intracellular calcium level when the macrophages were pretreated with pertussis toxin or genistein and subsequently challenged with cisplatin; whereas macrophages treated with cholera toxin showed a slight increase in intracellular calcium, which was significantly upregulated upon cisplatin treatment. Calcium-modulating agents EGTA, nifedipine, and TMB-8, and the calmodulin antagonist W-7, inhibited cisplatin-induced tumoricidal activity of murine BMDM. Supernatants collected from macrophages treated with cisplatin and EGTA, nifedipine, TMB-8, or W-7 demonstrated decreased TNF and IL-1 activity in comparison to supernatants collected from macrophages treated with cisplatin alone.