Fc gamma RIII mediates neutrophil recruitment to immune complexes: A mechanism for neutrophil accumulation in immune-mediated inflammation

Neutrophil accumulation is a hallmark of immune complex-mediated inflammato ry disorders. Current models of neutrophil recruitment envision the capture of circulating neutrophils by activated endothelial cells. We now demonstr ate that immobilized immune complexes alone support the rapid attachment of neutrophils, under physiologic flow conditions. Initial cell tethering req uires the low-affinity Fc gamma receptor IIIB (Fc gamma RIIIB), and the bet a (2) integrins are additionally required for the subsequent shear-resistan t adhesion. The attachment function of Fc gamma RIIIB may be facilitated by its observed presentation on neutrophil microvilli. In vivo, in a model of acute antiglomerular basement membrane nephritis in which immune complexes are accessible to circulating neutrophils, Fc gamma RIII-deficient mice ha d a significant reduction in neutrophil recruitment. Thus, the interaction of immune complexes with Fc gamma RIII may mediate early neutrophil recruit ment in immune complex-mediated inflammation.