Modulation ofLeishmania (L.) amazonensisGrowth inCultured Mouse Macrophages by Prostaglandins and Platelet Activating Factor

[摘要] The role of endogenously synthesized PAF and prostaglandins on theinfection of mouse macrophages byLetsbmanta (L.) amazonensiswasinvestigated, as well as the possible correlation between theeffects of these inflammatory mediators with nitric oxideproduction. It was found that pretreatment of macrophages with 10−5Mof the PAF antagonists, BN-52021 or WEB-2086, increasedmacrophage infection by 17 and 59%, respectively. Thecyclooxygenase inhibitor, indomethacin (10μg/ml), induced asignificant inhibition which was reversed by addition of PGE (10-3M) to the culture medium. These results suggested that the infectionof macrophages by leisbmanla is inhibited by PAF and enhanced byprostaglandins and that these mediators are produced by macrophagesduring this infection. This was confirmed by addition of thesemediators to the culture medium before infection; PAF (10−6, 10−9and 10−12M) reduced significantly the infection whereas PGE2(10−5M)induced a marked enhancement. This effect of exogenous PAF onmacrophage infection was reversed by the two PAF antagonists used inthis study as well as by the inhibitor of nitric oxide synthesis,L-arginine methyl ester (100 mM). Taken together the data suggestthat endogenous production of PAF and PGE2exert opposing effects onLesbmana–macrophage interaction and that nitric oxide may beinvolved in the augmented destruction of parasites induced by PAF.

[学科分类] 生理学与病理学