title: Extravasations and emigration of neutrophils to the inflammatory site depend on the interaction of immune-complex with Fcgamma receptors and can be effectively blocked by decoy Fcgamma receptors.
abstract: Extravasation and emigration of neutrophils to the site of inflammation are essential early steps in the initiation of many antibody-mediated autoimmune diseases. The Fc domains of cell bound autoantibodies or immune-complexes (IC) are capable of triggering the neutrophil emigration via complement and FcgammaRs-mediated mechanisms. To define the clinical relevance and the relative contribution of these 2 pathways in IC-mediated neutrophil emigration, we have neutralized the FcgammaR-binding activity of IC with a recombinant dimeric Fc receptor, CD16A-Ig, and investigated the early events of IC-induced inflammation in mice. Systemic administration of purified CD16A-Ig blocked IC-induced inflammation, mast- cell degranulation, and extravasation of neutrophils in a reversed Arthus reaction. Although the binding of CD16A-Ig to IC did not alter the complement-activating properties of IC, no evidence for complement-dependent neutrophil emigration was observed. These results suggest that interaction of IC with cells expressing FcgammaRs at the inflammatory site results in the secretion of chemoattractants, which mediate complement-independent emigration of neutrophils in this cutaneous acute inflammation model. Furthermore, blocking the interaction of IC to FcgammaRs expressed on inflammatory cells by administering high-avidity Fc fusion dimers of low-affinity FcgammaRs is an effective way of preventing IC-induced acute inflammation in autoimmune diseases.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Rangaiah
authors.initials: R
authors.lastname: Shashidharamurthy
authors.forename: Randolph A
authors.initials: RA
authors.lastname: Hennigar
authors.forename: Sebastien
authors.initials: S
authors.lastname: Fuchs
authors.forename: Purani
authors.initials: P
authors.lastname: Palaniswami
authors.forename: Melanie
authors.initials: M
authors.lastname: Sherman
authors.forename: Periasamy
authors.initials: P
authors.lastname: Selvaraj
mesh_terms: D000208:Acute Disease; D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D001183:Arthus Reaction / Q000188:drug therapy / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D002630:Chemotactic Factors / Q000276:immunology; D003167:Complement Activation / Q000187:drug effects; D003165:Complement System Proteins / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D051379:Mice; D020556:Neutrophil Infiltration / Q000187:drug effects* / Q000276:immunology; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology*
chemical_list: D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D002630:Chemotactic Factors; C496124:FCGR3A protein, human; D007074:Immunoglobulin G; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins; D003165:Complement System Proteins