Avaliação da modulação da infecção de macrófagos humanos com Leishmania (Viannia) braziliensis por fator ativador de plaquetas (PAF)

• Autor(a) principal: Borges, Arissa Felipe
• Data de Publicação: 2013
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UFG
• dARK ID: ark:/38995/00130000026k6
• Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/4532
• topic: Leishnânia; Macrófago humanos; Fator ativador de plaquetas; Leishmania braziliensis; Human macrophages; PAF; CIENCIAS DA SAUDE

The platelet activating factor (PAF) is produced by macrophages during inflammation and infection. The role of PAF in leishmaniasis, a disease caused by the protozoan Leishmania spp is not yet fully elucidated. This study was aimed to evaluate the modulation of human macrophage infection with L. (V.) braziliensis by PAF. Monocyte-derived macrophages were incubated with promastigote forms and the infection was assessed under light microscopy (infection index = % infected macrophages x the mean number of parasites per macrophage) after 4 h or 48 h incubation. The NBT assay was used to evaluate the production of superoxide anion. Treatment with PAF 10-10 M, 3 h before the addition of the parasites, increased infection index after 4 h of incubation (Medium vs PAF: 212 vs 324, p <0.05), whereas the infection decreased after 48 h of incubation when PAF was added together with parasites (554 vs 181, p <0.05). The effect of PAF seems to be on macrophages and not on parasites, since the treatment of parasites before incubation with the cells decreased the infection index after 4 h (p <0.05). It was observed that treatment of macrophages with rIFNg, PAF and LPS simultaneously intensified the decreasing of infection index, but the results were not significantly different of those from cultures treated with only PAF. Treatment of macrophages with a PAF antagonist, PCA 4248, 30 min before incubation with the parasites caused a significant increase of the infection index in a concentration-dependent manner (p <0.05) after 48 h. The effect of PCA 4248 was observed only when it was present during the first 4 h of incubation. The inhibition of the reactive oxygen intermediates (ROI) and nitric oxide (NO) production with apocynin and aminoguanidine, respectively, increased the infection (Medium vs apocynin: 200 vs 501; vs Aminoguanidine: 389, p <0.05). In parallel, it was showed that L. (V.) braziliensis induces the production of ROI (superoxide anion) which is further increased by exogenous or endogenous PAF. In conclusion, PAF modulates phagocytosis and increases the microbicidal activity depending on the concentration, contributing to the control of the human macrophage infection with L. (V.) braziliensis. The data showed that Leishmania (V.) braziliensis induces the production of ROI and NO in human macrophages, and suggested that PAF-enhanced microbicidal activity is mediated by an increased production of ROI. The data indicate that PAF activates human macrophages, and can play an important role in the control of the infection by L. (V.) braziliensis.