Submitted April 17, 2007
Accepted October 11, 2007
Extravasations and emigration of neutrophils to the inflammatory site depend on the interaction of immune-complex with Fc
receptors and can be effectively blocked by decoy Fc receptors
Rangaiah Shashidharamurthy, Randolph A Hennigar, Sebastien Fuchs, Purani Palaniswami, Melanie Sherman, and Periasamy Selvaraj*
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, United States
* Corresponding author; email: pselvar{at}emory.edu.
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 Fc
Rs-mediated mechanisms. To define the clinical relevance and the relative contribution of these two pathways in IC-mediated neutrophil emigration, we have neutralized the FcR-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 FcRs 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 FcRs expressed on inflammatory cells by administering high avidity Fc fusion dimers of low affinity FcRs is an effective way of preventing IC-induced acute inflammation in autoimmune diseases.
