Differential requirement of lipid rafts for Fc gamma RIIA mediated effector activities

Immunoglobulin G (IgG) dependent activities are important in host defense and autoimmune diseases. Various cell types including macrophages and neutrophils contribute to pathogen destruction and tissue damage through binding of IgG to Fc gamma receptors (Fc gamma R). One member of this family, Fc gamma RIIA, is a transmembrane glycoprotein known to mediate binding and internalization of IgG-containing targets. Fc gamma RIIA has been observed to translocate into lipids rafts upon binding IgG-containing targets. We hypothesize that lipid rafts participate to different extents in binding and internalizing targets of different sizes. We demonstrate that disruption of lipid rafts with 8 mM methyl-beta-cyclodextrin (M beta CD) nearly abolishes binding (91% reduction) and phagocytosis (60% reduction) of large IgG-coated targets. Conversely, binding and internalization of small IgG-complexes is less dependent on lipid rafts (49% and 17% inhibition at 8 mM M beta CD, respectively). These observations suggest that differences between phagocytosis and endocytosis may arise as early as the initial stages of ligand recognition. (C) 2010 Elsevier Inc. All rights reserved.