Macrophage Function in Tumor-Bearing Mice: Tumoricidal and Chemotactic Responses of Macrophages Activated by Infection with Mycobacterium Bovis, Strain BCG

Abstract

Abstract Peritoneal macrophages from mice with syngeneic transplantable footpad tumors were less responsive in vitro to chemotactic stimuli than were macrophages from mice without tumors. The macrophage chemotactic defect was about half the normal response and was evident in mice with nonpalpable 3 to 5-day tumors. Depressed macrophage chemotaxis persisted until the death of the mouse at 6 to 8 weeks. The number of peritoneal exudate cells elicited in tumor-bearing mice 8 to 14 days after intraperitoneal infection with BCG was also depressed. This inflammatory defect was detected 1 week after tumor transplantation and persisted for more than 5 weeks. The yield of peritoneal exudate macrophages induced by BCG infection in mice with tumors was about half the normal yield. In contrast to resident peritoneal macrophages, peritoneal exudate macrophages induced by BCG in tumor-bearing mice were as responsive to chemotactic stimuli as BCG-activated macrophages from control mice. BCG-activated macrophages from tumor-bearing or control mice were cytotoxic to tumor cells in vitro; no differences in tumoricidal responses of these BCG-activated macrophages were evident. The number of BCG organisms necessary to induce activated tumoricidal macrophages in mice with or without tumors was also identical. Peritoneal exudate macrophages from tumor-bearing mice infected with BCG at a dose that did not induce tumoricidal cells showed chemotactic defects similar to those of the resident macrophages. These results suggest that the response to BCG infection in tumor-bearing mice was defective. The defect was quantitative: a sequela of abnormal inflammatory responses. BCG-activated macrophages from tumor-bearing and control mice were functionally indistinguishable.