Studies of macrophage function in murine systemic lupus erythematosus. 4. Failure to reverse the defect in Fc-mediated phagocytosis and binding by in vitro stimulants or prostaglandins.
Previous studies have shown that resident peritoneal macrophages from mice with systemic lupus erythematosus (SLE) show defective Fc-mediated phagocytosis and binding of opsonized sheep erythrocytes (EA) in vitro. Possible causes of this defect in (NZB X NZW)F1 (B/W) mice were investigated. These included a maturational block in peritoneal macrophage differentiation, the production by peritoneal cells of a factor which inhibits Fc receptor expression and phagocytosis, and an abnormal response by macrophages of autoimmune mice to prostaglandins. Resident peritoneal macrophages of B/W mice did not show a maturational block since incubation with either (a) differentiating agents such as 4 beta-phorbol 12 beta-myristate 13 alpha acetate or retinoic acid, or (b) lymphokine (LK), prepared by Con A stimulation of mouse spleen cells, failed to enhance Fc-mediated phagocytosis and binding by B/W cells relative to controls. However, LK from B/W and B6AF1 cells stimulated Fc-mediated phagocytosis and binding by bone-marrow (BM)-derived macrophages of CBA/H mice; B/W LK also stimulated BM cells from B/W mice. Peritoneal cell supernatants did not inhibit phagocytosis of Fc receptor expression by BM-derived macrophages in vitro. Prostaglandin E treatment of peritoneal or BM-derived macrophages in vitro failed to restore decreased phagocytosis and binding of EA induced by culture in indomethacin and failed to stimulate phagocytosis by untreated cultures. The reason for the observed defect remains obscure.
D000818:Animals; D001854:Bone Marrow Cells; D007213:Indomethacin / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000503:physiopathology*; D008222:Lymphokines / Q000494:pharmacology; D008264:Macrophages / Q000503:physiopathology*; D051379:Mice; D008815:Mice, Inbred Strains; D010587:Phagocytosis; D011453:Prostaglandins / Q000494:pharmacology; D011961:Receptors, Fc / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology
D008222:Lymphokines; D011453:Prostaglandins; D011961:Receptors, Fc; D014212:Tretinoin; D013755:Tetradecanoylphorbol Acetate; D007213:Indomethacin