Cross-linking of immune complexes by human mononuclear phagocytes.
Incubation of immune complexes (IC) bound to plastic surfaces with human blood monocytes for 48 hours resulted in the cross-linking of a proportion of antibody molecules. This process was largely inhibited by the addition of sodium azide to the cultures. Cross-linking was defined as the inability of strong chaotropic solutions (3 M MgCl2 or 5 M guanidine) or acid pH (0.1 N HCl) to solubilize 125I-labeled rabbit anti-human serum albumin attached to plastic-bound antigen. Addition to the cultures of a suitable hydrogen donor such as catechol (0.5 mM) resulted in a large increase in cross-linking of IC. This process was shown to depend on the presence of viable phagocytic cells because incubation with dead monocytes or with viable T lymphocytes failed to induce cross-linking. Quantitation of rabbit immunoglobulin remaining in the wells by enzyme-linked immunoassay techniques excluded the possibility that the increase in 125I bound was merely due to a transiodination reaction. Experiments using various oxygen metabolite inhibitors and scavengers indicated that catechol-dependent protein cross-linking depended on the action of hydrogen peroxide and enzyme systems inhibitable by sodium azide, probably monocyte-peroxidase. Superoxide dismutase, 1O2, and OH X radical scavengers failed to inhibit cross-linking, whereas addition of catalase resulted in almost complete abolition of the process. These observations suggest that catechol-dependent cross-linking of IC may be due to oxidation of catechol to orthoquinone and that this strong oxidant is responsible for nonenzymic chemical action on proteins leading to intermolecular covalent bond formation. Cell-mediated protein cross-linking by oxidative mechanisms may be a prominent feature of drug-related reactions and of acute and chronic inflammatory processes in general. The possible mechanisms involved in catechol-dependent and -independent cross-linking of IC by human mononuclear phagocytes are discussed.
D000936:Antigen-Antibody Complex; D000937:Antigen-Antibody Reactions / Q000187:drug effects; D002374:Catalase / Q000494:pharmacology; D002396:Catechols / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D006801:Humans; D006859:Hydrogen / Q000494:pharmacology; D010586:Phagocytes / Q000276:immunology*; D013482:Superoxide Dismutase / Q000494:pharmacology
D000936:Antigen-Antibody Complex; D002396:Catechols; D003432:Cross-Linking Reagents; D006859:Hydrogen; D002374:Catalase; D013482:Superoxide Dismutase; C034221:catechol