Regulatory role of a peptide from the second constant domain of immunoglobulin G--II. In vitro effect on granuloma formation around S. mansoni eggs.
Previous studies have shown that hydrolysis of IgG by proteases secreted by S. mansoni schistosomula release peptidic fragments which inhibit various macrophage functions. Several peptides from the second constant domain of IgG reduced granuloma formation in vitro with spleen cells from mice infected by S. mansoni eggs of the parasite. The maximal inhibitory effect was obtained by the tripeptide Thr-Lys-Pro (TKP). Inhibition occurred at the early stage of the granulomatous response. Among the cells involved only the adherent cell population was inhibited by the peptide. In addition, TKP-inhibited macrophage migration towards soluble egg antigens (SEA), suggesting that the reduced granuloma reaction by TKP is the result of the interaction between the peptide and macrophages. Injection of TKP into infected mice reduced the in vitro granulomatous response obtained using their spleen cells. This suggests an in vivo interaction between TKP and cells from the monocyte lineage. Moreover, the substitution of TKP on its NH2 or COOH terminal (Acetyl-TKP and TKP-amide) did not affect its in vitro activity. The latter result is of particular importance in the in vivo application of the peptide, at present under investigation.
D000595:Amino Acid Sequence; D000818:Animals; D006099:Granuloma / Q000276:immunology; D007127:Immunoglobulin Constant Regions / Q000276:immunology; D007128:Immunoglobulin Fragments / Q000276:immunology*; D007142:Immunoglobulin gamma-Chains / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009842:Oligopeptides / Q000494:pharmacology*; D012550:Schistosoma mansoni; D012552:Schistosomiasis / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013329:Structure-Activity Relationship
D007127:Immunoglobulin Constant Regions; D007128:Immunoglobulin Fragments; D007142:Immunoglobulin gamma-Chains; D009842:Oligopeptides; C045468:threonyl-lysyl-proline