The trypanosomatid flagellar apparatus contains conventional and unique features, whose roles in infectivity are still enigmatic. Although the flagellum and the flagellar pocket are critical organelles responsible for all vesicular trafficking between the cytoplasm and cell surface, still very little is known about their roles in pathogenesis and how molecules get to and from the flagellar pocket. The ongoing analysis of the genome sequences and proteome profiles of Leishmania major and L infantum, Trypanosoma cruzi, T. brucei, and T. gambiensi ( www.genedb.org ), coupled with our own work on L. chagasi (as part of the Brazilian Northeast Genome Program- www.progene.ufpe.br ), prompted us to scrutinize flagellar genes and proteins of Leishmania spp. promastigotes that could be virulence factors in leishmaniasis. We have identified some overlooked parasite factors such as the MNUDC-1 (a protein involved in nuclear development and genomic fusion) and SQS (an enzyme of sterol biosynthesis), among the described flagellar gene families. A database concerning the results of this work, as well as of other studies of Leishmania and its organelles, is available at http://nugen.lcc.uece.br/LPGate . It will serve as a convenient bioinformatics resource on genomics and pathology of the etiological agents of leishmaniasis.
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.
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