Superoxide anion and hydrogen peroxide release by macrophages from mice treated with Nocardia rubra cell-wall skeleton: inhibition of macrophage cytotoxicity by a protease inhibitor but not by superoxide dismutase and catalase.

Peritoneal macrophages obtained from male BALB/c mice intraperitoneally injected with Nocardia rubra cell-wall skeleton (N-CWS) showed abundant superoxide anion and hydrogen peroxide release in response to opsonized zymosan used as a trigger. These N-CWS-induced macrophages also showed marked cytolytic activity against syngeneic Meth A fibrosarcoma targets. To examine the possible role of superoxide anion and/or hydrogen peroxide in the lysis of Meth A cells, N-CWS-induced macrophages were assayed with Meth A targets in the presence of superoxide dismutase, catalase, or both. However, addition of these agents to the assays, in doses which abolished detectable superoxide anion and/or hydrogen peroxide release from the effector cells, had no inhibitory effects on the cytotoxicity of N-CWS-induced macrophages. In contrast, both a protease inhibitor and actinomycin D could inhibit the cytolysis of Meth A targets by N-CWS-induced macrophages. These data raise the possibility that protease(s) rather than oxygen intermediates might be involved in the cytotoxicity of N-CWS-induced macrophages against tumor cells.