Role of Nitric Oxide on Human Schistosomiasis Mansoni: Upregulation ofin VitroGranuloma Formation byNω-Nitro-l-arginine Methyl Ester

Silva-Teixeira

Araújo-Filho

et al. 1999

Braz J Med Biol Res

Nitric oxide (NO) is an extremely important and versatile messenger in biological systems. It has been identified as a cytotoxic factor in the immune system, presenting anti-or pro-inflammatory properties under different circumstances. In murine monocytes and macrophages, stimuli by cytokines or lipopolysaccharide (LPS) are necessary for inducing the immunologic isoform of the enzyme responsible for the high-output production of NO, nitric oxide synthase (iNOS). With respect to human cells, however, LPS seems not to stimulate NO production in the same way. Addressing this issue, we demonstrate here that peripheral blood mononuclear cells (PBMC) obtained from schistosomiasis-infected patients and cultivated with parasite antigens in the in vitro granuloma (IVG) reaction produced more nitrite in the absence of LPS. Thus, LPS-induced nitrite levels are easily detectable, although lower than those detected only with antigenic stimulation. Concomitant addition of LPS and L-N-arginine methyl ester (L-NAME) restored the ability to produce detectable levels of nitrite, which had been lost with L-NAME treatment. In addition, LPS caused a mild decrease of the IVG reaction and its association with L-NAME was responsible for reversal of the L-NAME-exacerbating effect on the IVG reaction. These results show that LPS alone is not as good an NO inducer in human cells as it is in rodent cells or cell lines. Moreover, they provide evidence for interactions between LPS and NO inhibitors that require further investigation.

Section: Effects Of Lps On No Release and On Its Inhibition By L-namesupporting

confidence: 70%

“…Recently, we have reported that NO inhibition by L-N-arginine methyl ester (L-NAME) acted by exacerbating the IVG reaction (9). This led us to determine whether this effect would persist under additional circumstances.…”

Section: Introductionmentioning

confidence: 99%

Antigenic stimulation is more efficient than LPS in inducing nitric oxide production by human mononuclear cells on the in vitro granuloma reaction in schistosomiasis

Silva-Teixeira

Araújo-Filho

et al. 1999

Braz J Med Biol Res

“…However, NO appears to have anti-inflammatory or pro-inflammatory properties under different conditions (Kubes 1993). It has also been shown that inhibition of iNOS exacerbates the granulomatous reaction in vitro and this observation lead to the speculation of a probable regulatory role of NO in the development of chronic granulomatous inflammation (Oliveira et al 1998, Hesse et al 2001. Despite its potential for tissue damage by direct cytotoxic or cytostatic activity, NO appears to contribute to the maintenance of immunologic homeostasis through T-cell suppression or Th-cell differentiation (Bingisser et al 1998).…”

Section: Immune Response In Undernourished Mice Infected With S Mansonimentioning

confidence: 99%

Manson's schistosomiasis in the undernourished mouse: some recent findings

Coutinho

Mem. Inst. Oswaldo Cruz

Barros

et al. 2010

This paper deals with current knowledge of the interrelationships between Schistosoma infection and malnutrition. It emphasizes the relevance of these investigations in the face of dynamic and evolving changes occurring in population diets and changes in the epidemiological patterns of schistosomiasis in endemic countries. The paper further discusses the basis for continuing the studies on this subject and the reasons why it represents a misunderstood association. This review also focuses on the cellular and humoral immune responses in the undernourished mouse model infected with Schistosoma mansoni, with updated information on the immune response in wild-type and iNOS knockout mice concerning soluble egg antigen specific antibodies and kinetics of IFN-γ, IL-4, IL-10 and IL-13 cytokines, in the chronic phase of Manson's schistosomiasis. There is indication that schistosome-infected undernourished mice are able to develop a humoral immune response, but antibody titres are much lower than in the control animals. Cytokine production (IFN-γ, IL-4, IL-10) is lower in the undernourished mice, but as infection progresses to the chronic phase its kinetics run an antagonistic course when compared to that of well-nourished animals. Marked variation in the secretion of IL-13 (a fibrogenic cytokine) could explain why undernourished mice do not develop liver "pipe-stem" fibrosis described in previous papers on well-nourished animals

“…Recently we have described a regulatory role for NO on human schistosomiasis (Oliveira et al 1998) and specially with PIII, which induces higher in vitro NO production by human mononuclear cells (Oliveira et al unpublished observations). Attempting to further investigate whether immunization with PIII would affect the in vitro NO production, we cultured spleen cells (obtained from mice of experimental trials) with S. mansoni antigens and analyzed their nitrite releasing capacity.…”

mentioning

confidence: 96%

Immunization with PIII, a fraction of Schistosoma mansoni soluble adult worm antigenic preparation, affects nitric oxide production by murine spleen cells

Mem. Inst. Oswaldo Cruz

Carmo

Silva-Teixeira

et al. 1998