Oxidative cross-linking of immune complexes by human polymorphonuclear leukocytes.
Incubation of human serum albumin-anti-human serum albumin immune complexes bound to a plastic surface, with human polymorphonuclear leukocytes for 1 h at 37 degrees C resulted in covalent cross-linking of 8.5% +/- 0.5 of the complexes, corresponding to a minimum rate of 700 antibody molecules per cell per minute. Similar results were obtained with IgG-anti-IgG and type II collagen-anticollagen II human antibodies. Cross-linking was defined as the antibody remaining attached to plastic-bound antigen after extraction with 3 M MgCl2 and 0.1 N HCl solutions. The effects of addition of oxygen radical scavengers, heme-enzyme inhibitors, and omission of Cl- indicated that the cross-linking process was mediated by the myeloperoxidase-H2O2-Cl- system. Cross-linking was also obtained with cell lysates, polymorphonuclear granules, and purified human myeloperoxidase in the presence of a steady flux of H2O2 provided by glucose oxidase-glucose. Cross-linking by the cell-free systems was also abolished by sodium azide or omission of chloride ions. Cross-linked immune complexes were also generated by incubation with 20 to 50 microM solutions of freshly distilled hypochlorous acid. Addition of 10 mM hypochlorous acid to soluble IgG resulted in the formation of protein precipitates insoluble in 5 M guanidine, 0.1 N HCl, or boiling 2.3 M sodium dodecyl sulfate-1.4 M 2-mercaptoethanol. The remaining soluble IgG contained fluorescent high molecular aggregates (ex: 360 nm; em: 454 nm). Oxidative cross-linking of antigen-antibody molecules, and of immune complexes to connective tissue macromolecules may play a pathogenic role in acute and chronic inflammatory processes.
Jasin
H E
HE
Department of Internal Medicine, Southwestern Medical School, Dallas, Texas 75235.
D000936:Antigen-Antibody Complex / Q000378:metabolism*; D002712:Chlorides / Q000097:blood; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood; D006997:Hypochlorous Acid / Q000097:blood; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption; D009195:Peroxidase / Q000097:blood; D012709:Serum Albumin / Q000276:immunology / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism
D000936:Antigen-Antibody Complex; D002712:Chlorides; D012709:Serum Albumin; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D009195:Peroxidase; D010100:Oxygen