title: Ligation of CR1 attenuates Fc receptor-mediated myeloperoxidase release and HOCl production by neutrophils.
abstract: Surface adherent immunoglobulins are potent stimuli for inducing neutrophil release of myeloperoxidase and production of hypochlorous acid (HOCl), an oxidant that promotes activity of neutrophil proteases. Opsonization of surface adherent IgG (SAIgG) by complement results in attenuation of these responses, despite augmenting neutrophil production of superoxide and release of specific granule enzymes. The role of complement receptor ligation in modulating Fc receptor-triggered myeloperoxidase release and HOCl production by neutrophils was determined by incubating neutrophils with SAIgG in the presence of complement receptor ligating antibody reagents. Ligation of CR1 by F(ab')2 derived from CR1 specific monoclonal antibody (mAb 543) resulted in significant attenuation of surface-associated IgG (SAIgG)-induced release of myeloperoxidase and HOCl production but did not result in attenuation of SAIgG-induced superoxide or hydrogen peroxide production; ligation of CR1 by mAb 543 F(ab')2 also attenuated surface adherent IgA-induced myeloperoxidase release and HOCl production. HOCl production was not significantly attenuated when neutrophils were activated with SAIgG in the presence of surface adherent C1q or when CR3 was ligated by F(ab')2 derived from mAb having specificity for the CD11b (mAb M1/70) or CD18 (mAb TS1) subunits of CR3. These results indicate that ligation of CR1 on neutrophils by C3b fixed to IgG may alter signal transduction events linking ligation of neutrophil Fc receptors to cellular events required for release of myeloperoxidase and generation of HOCl.
authors.affiliation: Division of Clinical Immunology and Rheumatology, The University of Alabama at Birmingham, Department of Veterans Affairs, 35233, USA.
authors.forename: T
authors.initials: T
authors.lastname: Sambandam
authors.forename: W W
authors.initials: WW
authors.lastname: Chatham
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000502:physiology; D018821:CD18 Antigens / Q000276:immunology; D002352:Carrier Proteins; D002478:Cells, Cultured; D006801:Humans; D018960:Hyaluronan Receptors; D006861:Hydrogen Peroxide / Q000378:metabolism; D006997:Hypochlorous Acid / Q000378:metabolism*; D007140:Immunoglobulin Fab Fragments / Q000502:physiology; D016177:Macrophage-1 Antigen / Q000276:immunology; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D018375:Neutrophil Activation / Q000502:physiology*; D009504:Neutrophils / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism*; D011951:Receptors, Complement / Q000502:physiology*; D017463:Receptors, Complement 3b / Q000276:immunology; D011961:Receptors, Fc / Q000502:physiology*; D017452:Receptors, IgG / Q000502:physiology; D013481:Superoxides / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C087299:C1QBP protein, human; D018821:CD18 Antigens; D002352:Carrier Proteins; C036832:Fc(alpha) receptor; D018960:Hyaluronan Receptors; D007140:Immunoglobulin Fab Fragments; D016177:Macrophage-1 Antigen; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D011961:Receptors, Fc; D017452:Receptors, IgG; C032402:complement 1q receptor; D013481:Superoxides; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D009195:Peroxidase