Selective inhibition of IgG-mediated phagocytosis in gelsolin-deficient murine neutrophils

Phagocytosis and the microbicidal functions of neutrophils require dynamic changes of the actin cytoskeleton. We have investigated the role of gelsoli n, a calcium-dependent actin severing and capping protein, in peripheral bl ood neutrophils from gelsolin-null (Gsn(-)) mice. The phagocytosis of compl ement opsonized feast was only minimally affected. In contrast, phagocytosi s of IgG-opsonized yeast was reduced dose to background level in Gsn(-) neu trophils. Thus, gelsolin is essential for efficient IgG- but not complement -mediated phagocytosis. Furthermore, attachment of IgG-opsonized yeast to G sn- neutrophils was reduced (similar to 50%) but not to the same extent as ingestion (similar to 73%), This was not due to reduced surface expression of the Fc gamma -receptor or its lateral mobility, This suggests that attac hment and ingestion of IgG-opsonized yeast by murine neutrophils are actin- dependent and gelsolin is important for both steps in phagocytosis. We also investigated granule exocytosis and several steps in phagosome processing, namely the formation of actin around the phagosome, translocation of granu les, and activation of the NADPH-oxidase. All these functions were normal i n Gsn- neutrophils, Thus, the role of gelsolin is specific for IgG-mediated phagocytosis. Our data suggest that gelsolin is part of the molecular mach inery that distinguishes complement and IgG-mediated phagocytosis. The latt er requires a more dynamic reorganization of the cytoskeleton.