Defective Fc Receptor-Mediated Phagocytosis in C3H/HeJ Macrophages

Abstract Macrophages derived from LPS-unresponsive C3H/HeJ mice lose their ability to phagocytose opsonized SRBC (EA) after 24 hr of in vitro culture, whereas macrophages from normal mice exhibit a marked increase in phagocytosis of EA under the same culture conditions. Defective phagocytosis is not due to a decrease in macrophage number or viability and appears to be specific for Fc receptor-mediated phagocytosis, since phagocytosis of latex particles by C3H/HeJ macrophages is normal. The phagocytic defect appears to be due to a decrease in the binding ability or number of Fc receptors, since C3H/HeJ macrophages exhibit a loss of Fc binding ability that parallels the loss in their phagocytic ability. Cultured macrophages from LPS responsive (C3H/HeN) mice maintain their ability to bind EA after 48 hr culture. This Fc receptor defect appears to be secondary to a failure of C3H/HeJ macrophages to maintain a differentiated state in vitro, since induction of differentiation of C3H/HeJ macrophages with the supernatant derived from Con A-treated spleen cells (CS) results in an almost complete restoration of both their ability to bind and phagocytose EA. The activity of CS appears to be due to a lymphokine, since it is not present in the culture supernatants of unstimulated spleen cells and is not produced by Con A alone. These findings emphasize the close association between the induction of macrophage differentiation and the sensitivity of these cells to LPS. Furthermore, they suggest that one function of the Lps gene may be to regulate the ability of cells to respond to physiologic differentiation signals in addition to or instead of lipid A.