Nitric oxide-mediated immune complex-induced prostaglandin E(2) production by peripheral blood mononuclear cells of humans infected with Schistosoma mansoni.
Granuloma reaction around Schistosoma mansoni eggs is the prominent lesion in human schistosomiasis. Studies have suggested the involvement of a series of suppressive mechanisms in the control of this reaction. Using an in vitro model of granuloma formation, we have shown that immune complexes (IC) isolated from sera of chronic intestinal schistosomiasis patients were able to reduce granulomatous reaction developed against soluble egg antigen-conjugated polyacrylamide beads. In this system, the role of the l-arginine-nitric oxide (NO) pathway in the formation of prostaglandin E(2) (PGE(2)) by human peripheral blood mononuclear cells (PBMC) of patients infected with schistosomiasis was investigated using IC. Preincubation of PBMC with IC produced a significant increase of both nitrite and PGE(2) levels in the cell supernatant. This effect was inhibited by coincubation of cells with Nomega-nitro-l-arginine methyl ester (L-NAME), a NO synthase inhibitor, showing that the release of PGE(2) subsequent to IC stimulation was driven by NO. The inhibitory effect of L-NAME on PGE(2) release by IC-treated PBMC was reversed by sodium nitroprusside, a known NO donor. Our results indicate that NO could be an important second signal for the stimulation of PGE(2) production induced by IC in PBMC from human schistosomiasis patients.
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Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
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D000293:Adolescent; D000328:Adult; D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis*; D006099:Granuloma / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000276:immunology* / Q000378:metabolism; D012550:Schistosoma mansoni / Q000276:immunology; D012555:Schistosomiasis mansoni / Q000097:blood / Q000276:immunology*
D000936:Antigen-Antibody Complex; D009569:Nitric Oxide; D015232:Dinoprostone; D019331:NG-Nitroarginine Methyl Ester