Differential requirement of lipid rafts for FcγRIIA 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 Fcγ receptors (FcγR). One member of this family, FcγRIIA, is a transmembrane glycoprotein known to mediate binding and internalization of IgG-containing targets. FcγRIIA 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 8mM methyl-β-cyclodextrin (MβCD) 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 8mM MβCD, respectively). These observations suggest that differences between phagocytosis and endocytosis may arise as early as the initial stages of ligand recognition.
Vieth
Joshua A
JA
Department of Medical Microbiology and Immunology, University of Toledo College of Medicine, Toledo, OH 43614, USA.
Kim
Moo-Kyung
MK
Pan
Xiao Qing
XQ
Schreiber
Alan D
AD
Worth
Randall G
RG
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004705:Endocytosis / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D021962:Membrane Microdomains / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology*; D011485:Protein Binding; D017452:Receptors, IgG / Q000276:immunology* / Q000378:metabolism; D047392:beta-Cyclodextrins / Q000494:pharmacology
C080568:Fc gamma receptor IIA; D007074:Immunoglobulin G; D008024:Ligands; D017452:Receptors, IgG; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin