Induction of nitric oxide production by the peritoneal macrophages after intraperitoneal or subcutaneous transplantation of AK-5 tumor

We have investigated the role of host macrophages in the activation of effector functions in addition to their direct role in the induction of tumor cell death. Peritoneal macrophages from sc tumor-bearing animals were in an activated state and induced NO-mediated apoptotic death in AK-5 tumor cells. They also showed overexpression of inducible nitric oxide synthase both at the transcript and at the enzyme levels. However, macrophages from the ip tumor-bearing animals showed suppression of activation especially when the tumor load was high, suggesting thereby tumor-induced suppression of macrophage activation in ip tumor-transplanted hosts. Suppression of macrophage activation was also observed upon coculture of peritoneal macrophages with tumor cells in vitro. These studies suggest an important role played by the host peritoneal macrophages in the regression of AK-5 tumor. They also indicate suppression of macrophage activation by the tumor cells. (C) 1998 Academic Press.