Extravasations and emigration of neutrophils to the inflammatory site depend on the interaction of immune-complex with FcY receptors and can be effectively blocked by decoy FcY receptorsBlood
AbstractExtravasation 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.
Citation InformationRangaiah Shashidharamurthy, Randolph A. Hennigar, Sebastian Fuchs, Purani Palaniswami, et al.. "Extravasations and emigration of neutrophils to the inflammatory site depend on the interaction of immune-complex with FcY receptors and can be effectively blocked by decoy FcY receptors" Blood Vol. 111 Iss. 2 (2008) p. 894 - 904
Available at: http://works.bepress.com/rangaiah_shashidharamurthy/14/