Activation of human granulocytes by intravenous immunoglobulin preparations is mediated by FcgammaRII and FcgammaRIII receptors.
Previous studies from our laboratory have shown that i.v. Ig (IVIG) exposure triggers superoxide anion (O2) generation by and increases bactericidal capacity of human blood granulocytes. However, the molecular interactions between IVIG and granulocytes have not been evaluated before. The objective of this study was to investigate the role of FcgammaRII and FcgammaRIII receptors in the immunomodulatory effects of IVIG concentrates on granulocytes. We found that four different IVIG preparations (concentration range, 1-10 mg/mL) shared the ability to stimulate O2- release in vitro by granulocytes in a dose-dependent manner. Dimers fractionated from IVIG were significantly more potent in inducing activity of the respiratory burst than were monomers. MAb (concentration range, 0.1-10 microg/mL) specific for FcgammaRII and FcgammaRIII receptors inhibited the IVIG-induced O2- release, with a more profound inhibitory effect observed with anti-FcgammaRIII. These findings suggest the involvement of Fcgamma receptors in triggering O2- release by granulocytes exposed to IVIG. We also report that IVIG added to granulocyte suspensions elicited a rapid and vigorous increase in the concentration of cytosolic free calcium, a finding suggesting direct activation and not priming of granulocytes by IVIG through FcgammaRII and FcgammaRIII receptors. The in vitro effects described here might occur in patients treated with IVIG and may, in part, be responsible for inflammatory reactions evoked by infused Ig concentrates as well as the immunomodulatory effect of Ig in patients with autoimmune and inflammatory diseases.
Nemes
E
E
Department of Infectology and Pediatric Immunology, Medical and Health Science Center University of Debrecen, Hungary.
Teichman
F
F
Roos
D
D
Maródi
L
L
D000911:Antibodies, Monoclonal / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D006098:Granulocytes / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage; D008213:Lymphocyte Activation; D017452:Receptors, IgG / Q000276:immunology*; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D016756:Immunoglobulins, Intravenous; D017452:Receptors, IgG; D002118:Calcium