Extravasations and emigration of neutrophils to the inflammatory site depend on the interaction of immune-complex with Fcγ receptors and can be effectively blocked by decoy Fcγ receptors

Extravasation and emigration of neutrophils to the site of inflammation are essential early steps in the initiation of many anti body-mediated autoimmune diseases. The Fc domains of cell bound autoanti-bodies or immune-complexes (IC) are capable of triggering the neutrophil emigration via complement and Fc gamma Rs-mediated mechanisms. To define the clinical relevance and the relative contribution of these 2 pathways in IC-mediated neutrophil emigration, we have neutralized the Fc gamma R-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 Fc gamma Rs 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 Fc gamma Rs expressed on inflammatory cells by administering high-avidity Fc fusion dimers of low-affinity Fc gamma Rs is an effective way of preventing IC-induced acute inflammation in autoimmune diseases.