Alpha-1-antitrypsin-induced inhibition of complement-dependent phagocytosis

In a previous investigation, inhibition of complement-dependent rosette formation by alpha 1-antitrypsin (α 1-AT) was observed, and it was demonstrated that α 1-AT interacts through its carbohydrate portion with C3 and its fragments. In the present study, the effect of α 1-AT on the complement-receptor-mediated phagocytosis by human peripheral blood monocytes was examined. Purified α 1-AT inhibited in a dose-dependent manner phagocytosis of C3-carrying yeast particles. Inhibition was selective, concerned only C3-receptor-mediated phagocytosis, neither Fc-receptor-mediated phagocytosis nor uptake of untreated yeast particles was blocked by α 1-AT. It was demonstrated that α 1-AT exerted its inhibitory effect through binding to C3-carrying particles. The activity of α 1-AT towards C3 and fragments of C3 was not mediated by its antiprotease effect, but by its carbohydrate moiety. This finding suggests that α 1-AT may have an impact on various immune functions involving complement receptors.