Generation of IgG aggregates by the myeloperoxidase-hydrogen peroxide system.
Incubation of native human 125I-IgG with polymorphonuclear neutrophil (PMN) peroxidase-containing granules or with purified myeloperoxidase (MPO) in the presence of H2O2 and a suitable hydrogen donor such as catechol generated large amounts of heavy IgG aggregates. Short-term incubation (15 to 60 min) of native 125I-IgG (400 microgram) with MPO-containing granules or with purified MPO (1.5 microgram) in the presence of H2O2 (0.036 to 0.36 mumol) and catechol (0.2 mumol) resulted in the generation of 8 to 100 microgram of heavy IgG aggregates (3 X 10(5) to 4 X 10(6) daltons). Aggregate formation was completely abolished by the omission of H2O2 or catechol, and by the addition of catalase, sodium azide, or cyanide. IgG aggregates were also generated with tyrosinase, tyrosine, and atmospheric oxygen. These results indicate that aggregation was due to MPO-H2O2-mediated oxidation of catechol to orthoquinone, which was deemed to be directly responsible for cross-linking by non-enzymic biochemical reactions. The IgG aggregates generated were shown to behave as typical immune complexes in that they consumed C, were detected by the solid-phase C1q and Raji cell assays, and were precipitable by monoclonal rheumatoid factor. This nonspecific oxidative protein-aggregation reaction may play an important role in the pathogenesis of tissue injury in acute and chronic inflammatory processes and in drug reactions. It could also provide an explanation for the frequent detection of circulating immune complex-like material in a large variety of acute and chronic inflammatory states.
D000818:Animals; D003594:Cytoplasmic Granules / Q000276:immunology / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood*; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis*; D046911:Macromolecular Substances; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D009195:Peroxidase / Q000097:blood*; D010544:Peroxidases / Q000097:blood*
D007074:Immunoglobulin G; D046911:Macromolecular Substances; D006861:Hydrogen Peroxide; D010544:Peroxidases; D009195:Peroxidase