Activation of human granulocytes by intravenous immunoglobulin preparations is mediated by Fc gamma RII and Fc gamma RIII receptors

Previous studies from our laboratory have shown that i.v. Ig (IVIG) exposur e triggers superoxide anion (O-2(-)) generation by and increases bactericid al capacity of human blood granulocytes. However, the molecular interaction s between IVIG and granulocytes have not been evaluated before. The objecti ve of this study was to investigate the role of Fc gamma RII and Fc gamma R III receptors in the immunomodulatory effects of IVIG concentrates on granu locytes. We found that four different IVIG preparations (concentration rang e, 1-10 mg/mL) shared the ability to stimulate O-2(-) release in vitro by g ranulocytes in a dose-dependent manner. Dimers fractionated from IVIG were significantly more potent in inducing activity of the respiratory burst tha n were monomers. MAI, (concentration range, 0.1-10 mu g/mL) specific for Fc gamma RII and Fc gamma RIII receptors inhibited the IVIG-induced 0(2)(-) r elease, with a more profound inhibitory effect observed with anti-Fc gamma RIII. These findings suggest the involvement of Fc gamma receptors in trigg ering O-2(-) release by granulocytes exposed to IVIG. We also report that I VIG added to granulocyte suspensions elicited a rapid and vigorous increase in the concentration of cytosolic free calcium, a finding suggesting direc t activation and not priming of granulocytes by IVIG through Fc gamma RII a nd Fc gamma RIII receptors. The in vitro effects described here might occur in patients treated with IVIG and may, in part, be responsible for inflamm atory reactions evoked by infused Ig concentrates as well as the immunomodu latory effect of Ig in patients with autoimmune and inflammatory diseases.