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 FcYRs-mediated mechanisms. To define the clinical relevance and the relative contribution of these 2 pathways in IC-mediated neutrophil emigration, we have neutralized the FcYR-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 FcYRs 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 FcYRs expressed on inflammatory cells by administering high-avidity Fc fusion dimers of low-affinity FcYRs is an effective way of preventing IC-induced acute inflammation in autoimmune diseases.
Available at: http://works.bepress.com/rangaiah_shashidharamurthy/14/