Studies of Macrophage Function in Murine Systemic Lupus Erythematosus. 3. The Nature, Anatomical Location, and Reversibility of the Phagocytic Defect

The defect in phagocytosis and binding of antibody‐coated sheep erythrocytes (EA) by peritoneal macrophages of (NZB × NZW)F1 or B/W mice is not intrinsic, but is related to the development of the autoimmune disease process. The defect appears to be confined to peritoneal macrophages, since bone marrow (BM)‐derived macrophages have normal to elevated activities in vitro. The peritoneal macrophage defect is not due to blockade of Fc receptors in vivo, as shown by long‐term culture or recovery of phagocytic and binding activities after removal of Fc receptors by pronase, but represents a reduced number of receptors with slightly delayed turnover. The defect can be reversed by elicitation of activated macrophages with Corynebacterium parvum, thioglycollate, or proteose peptone in vivo. Normal Fc‐mediated phagocytosis and binding by BM‐derived macrophages cultured from untreated autoimmune mice is enhanced by pretreatment of mice with C. parvum, thioglycollate, or proteose peptone. The cause of the defect in Fc‐mediated phagocytosis by resident peritoneal macrophages of autoimmune mice was not ascertained; it may be due to abnormal macrophage kinetics or to the local effects of lymphokines released as a result of other autoimmune changes.