Macrophage function in tumor-bearing mice: Dissociation of phagocytic and chemotactic responsiveness

Abstract

Macrophage function in mice with tumors was examined by two in vitro assays: chemotaxis to lymphocyte- or serum-derived stimuli and phagocytosis of 51Cr-labeled IgG coated sheep erythrocytes ( 51Cr-EAIgG). Resident peritoneal macrophages from mice with intrafootpad syngeneic fibrosarcomas were less responsive to chemotactic stimuli than macrophages from control mice. Chemotactic responses were depressed to about half of normal within 3 days of tumor transplantation and remained depressed until death of the mouse by 6–8 weeks. In contrast to this persistent depression of macrophage chemotaxis, phagocytosis of 51Cr-EAIgG was markedly increased in tumorbearing mice. Macrophage uptake of 51Cr-EAIgG was 4–5 fold greater than normal within 1 week of tumor transplantation, progressively decreased to normal levels by 2 weeks and remained normal through 4 weeks. Increased phagocytic capacity of macrophages from mice with tumors reflected both increased numbers of phagocytic cells and increased numbers of erythrocytes phagocytized per cell. A similar increase in macrophage phagocytosis was observed with cells from mice bearing another tumor but not from mice treated with syngeneic spleen cells, medium or mineral oil. Thus, growing tumors induce significant alterations in mononuclear phagocyte function. Changes observed in vitro with macrophages from tumor-bearing mice may provide cellular mechanisms for the abnormal phagocytic and inflammatory responses of cancer patients.