Nitric oxide-mediated immune complex-induced prostaglandin E2 production by peripheral blood mononuclear cells of humans infected with Schistosoma mansoni.

Abstract

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 Larginine– nitric oxide (NO) pathway in the formation of prostaglandin E2 (PGE2) 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 PGE2 levels in the cell supernatant. This effect was inhibited by coincubation of cells with Nv-nitro-L-arginine methyl ester (L-NAME), a NO synthase inhibitor, showing that the release of PGE2 subsequent to IC stimulation was driven by NO. The inhibitory effect of L NAME on PGE2 release by ICtreated 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 PGE2 production induced by IC in PBMC from human schistosomiasis patients.