Macrophage handling of soluble immune complexes: evaluation of mechanisms involved in the selective clearance of complexes from the circulation.
The binding and release of soluble guinea pig IgG2-containing DNPBSA-anti-DNP complexes and antigen-free, covalently-linked anti-DNP IgG2 oligomers of similar size, by guinea pig peritoneal macrophages, has been examined in the absence and presence of monomeric IgG2, of unrelated antibody specificity, or the monovalent hapten, DNP lysine. Complex binding was found to differ from the binding of the oligomers in that it was about twice as efficient and was essentially irreversible even in the presence of an inhibitor of ingestion, cytochalasin B. On the other hand, quantitative complex release could be achieved, in the presence of the ingestion inhibitor, by including 1.5mM DNP lysine in the medium. Complex handling by macrophages at 37 degrees C was also examined in the presence of monomeric IgG2, at its serum concn, and in the absence and presence of cytochalasin B. Inhibiting ingestion did not impair the capacity of the macrophages to take up complexes under these conditions. On the basis of these findings and previous reports that complexes bound to a receptor-bearing membrane undergo additional antibody-antigen bond formation [Dower et al., Biochemistry 20, 6326-6334 (1981a) and Leslie, Protides biol. Fluids 29, 431-434 (1982)] it is proposed that complex aggregation at the phagocyte surface may constitute the critical irreversible event required for the selective clearance of complexes in vivo. Other biological implications of receptor-mediated complex aggregation are also discussed.
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D001667:Binding, Competitive; D002478:Cells, Cultured; D003571:Cytochalasin B / Q000494:pharmacology; D006168:Guinea Pigs; D007074:Immunoglobulin G / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism
D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; C007493:epsilon-dinitrophenyllysine; D003571:Cytochalasin B; D008239:Lysine