Endogenous interferon production by endotoxin-responsive macrophages provides an autostimulatory differentiation signal.
Previous studies have demonstrated that peritoneal macrophages (resident or thioglycolate-induced) derived from mouse strains fully responsive to gram-negative endotoxins continue to differentiate in vitro, as evidenced by an increased capacity to phagocytose via the Fc receptor with time in culture. In contrast, macrophages derived from endotoxin-hyporesponsive mouse strains (e.g., C3H/HeJ or C57BL/10ScN) exhibit no such increase in phagocytic capacity, and, in fact, significantly lose the capacity to phagocytose particles opsonized with immunoglobulin G with time in culture. This defect was found to be fully correctable by the addition to the cultures of an exogenous source of alpha, beta, or gamma interferon. In this study, we compared C3H/HeN (endotoxin-responsive) and C3H/HeJ (endotoxin-responsive) and C3H/HeJ (endotoxin-hyporesponsive) macrophages in an attempt to elucidate the mechanism responsible for this difference in phagocytic (differentiative) potential. The following observations support the hypothesis that endotoxin-responsive macrophages, in contrast to endotoxin-hyporesponsive macrophages, produce significantly higher levels of an autostimulatory differentiation signal that appears to be macrophage-derived interferon. (i) Anti-alpha/beta-interferon antibody greatly reduces the ability of C3H/HeN macrophages to phagocytose opsonized erythrocytes: (ii) C3H/HeJ macrophages can be made more phagocytic by coculture with C3H/HeN macrophages or by treatment with supernatants derived from C3H/HeN macrophage cultures; and (iii) C3H/HeN macrophages spontaneously lose Mac-1 antigen with time in culture. C3H/HeJ macrophages must be interferon-treated to be equivalently down-regulated.
D000818:Animals; D000937:Antigen-Antibody Reactions; D000954:Antigens, Surface / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured; D004731:Endotoxins / Q000276:immunology; D007370:Interferon Type I / Q000276:immunology*; D016177:Macrophage-1 Antigen; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains / Q000276:immunology; D010587:Phagocytosis; D011961:Receptors, Fc / Q000276:immunology
D000954:Antigens, Surface; D004731:Endotoxins; D007370:Interferon Type I; D016177:Macrophage-1 Antigen; D011961:Receptors, Fc