Modulation of neutrophil Fc and C3b receptors. Relationship with the phagocytic process and activation of the respiratory burst.

Abstract

The effect of the interaction between human neutrophils and aggregated IgG on the expression of the receptors for the Fc portion of IgG (FcR) and for the C3b (C3R) has been investigated. Incubation of neutrophils with the appropriate concentrations of aggregated IgG at 37°C caused the loss of both the FcR and the C3R. This loss (modulation) was energy dependent (i.e., did not take place in cells incubated in the cold) and irreversible in that neutrophils did not reexpress either of the two receptors even upon prolonged incubation in vitro. The mechanisms leading to the modulation of FcR and C3R were different. FcR modulation was independent of the activation of the respiratory burst, since it occurred also in neutrophils from chronic granulomatous disease patients and was not induced by treatment of normal neutrophils with drugs such as phorbol myristate acetate (PMA), known to activate the respiratory burst. The FcR modulation was rather related to the redistribution (“capping”) and endocytosis of the FcR induced by the interaction with aggregated IgG. This possibility was supported by the finding that FcR modulation was blocked by inhibitors of phagocytosis and by the observation that aggregated IgG, tagged with a fluorescent dye, were “capped” and subsequently endocytosed by metabo'lically active cells. Modulation of C3R was dependent upon the activation of the respiratory burst induced by the interaction of aggregated IgG with the neutrophils. This hypothesis was also supported by the finding that the modulation of C3R was induced by treatment of the cells with PMA and did not occur in chronic granulomatous disease neutrophils treated with aggregated IgG or PMA. Furthermore the modulation of C3R was inhibited by the addition of catalase, suggesting that such modulation was consequent to the damaging effect of the oxygen active by-products on the receptor structures. In addition to the C3R modulation described above, another type of C3R loss was observed. This occurred in chronic granulomatous disease (CGD) neutrophils following interaction with the appropriate antigen-antibodycomplement complexes. In these cells, phagocytocis of the complexes caused a concomitant modulation of the C3R that was possibly related to the redistribution and endocytosis of the C3R structures.