Differential modulation of macrophage membrane markers by interferon: analysis of Fc and C3b receptors, Mac-1 and Ia antigen expression.

Abstract

The role of interferon (IFN) as a specific modulator of macrophage receptor and cell surface antigen expression has only recently been established. We previously demonstrated that macrophages derived from thioglycollate-treated C3H/HeJ mice provide an extremely sensitive model for analyzing the induction of enhanced Fc receptor capacity on treatment with IFN. Macrophage cultures treated with murine β IFN or γ IFN preparations were found to exhibit a dose-dependent increase in the ability to bind and phagocytose sheep erythrocytes coated with rabbit IgG antibodies (EAIgG). We have since found that highly purified β IFN (5 x 108 U/mg) induced an increase in both the number and density of IgG Fc receptors which correlates well with the enhanced ability of IFN-treated cells to bind and phagocytose sheep erythrocytes opsonized with either monoclonal IgG2a or IgG2b antibodies. These findings were confirmed using recombinant α IFN. We have also examined the ability of IFN to modulate other macrophage surface markers. Since the expression of Fc receptors for IgG was clearly augmented, we also measured the ability of IFN-treated cultures to bind and phagocytose sheep erythrocytes which were treated first with an IgM antierythrocyte antibody and secondarily with C5-deficient mouse serum (EAIgMC). Erythrocytes opsonized in this fashion have been used traditionally to assess binding and phagocytosis through the C3b receptor. Treatment of macrophages with β IFN results in a marked increase in the ability of these cultures to bind, but not phagocytose, EAIgMC. Further analysis indicated that the increased capacity to bind EAIgMC paralleled an increase in the capacity to bind erythrocytes opsonized with IgM only (EAIgM). Thus, IFN augments binding of EAIgMC through an apparent increase in IgM receptor capacity, rather than an increase in C3b receptors. We next examined the ability of IFN to regulate the expression of two different macrophage surface antigens, Mac-1 and Ia. Mac-1 is expressed predominantly on relatively immature macrophages. On exposure to in vitro, the expression of Mac-1 is down-regulated. Finally, we examined the ability of highly purified β IFN and recombinant α IFN to induce the expression of Ia antigens. Like C3b receptors, Ia antigen expression is associated with macrophages which are more highly differentiated. IFN failed to induce the expression of Ia antigens under conditions where Fc receptor expression was significantly enhanced. These findings strongly support the role of interferon as a differential modulator of macrophage cell surface antigens and receptors, and suggests that IFN may play a role as an early signal in a progressive sequence of macrophage differentiation.