Modulation of Leishmania (L.) amazonensis Growth inCultured Mouse Macrophages by Prostaglandins and Platelet Activating Factor

Abstract

Ttm role of endogenously synthesized PAF and prostaglandins on the infection of mouse macrophages by Letsbmanta (L) amazonensis was investigated, as well as the possible correlation between the effects of these inflammatory mediators with nitric oxide production. It was found that pretreatment of macrophages with 10-M of the PAF antagonists, BN-52021 or WEB-2086, increased macrophage infection by 17 and 59%, respectively. The cyclooxygenase inhibitor, indomethacin (10 g/ml), induced a significant inhibition which was reversed by addition of PGE (10 -3 M) to the culture medium. These results suggested that the infection of macrophages by leisbmanla is inhibited by PAF and enhanced by prostaglandins and that these mediators are produced by macrophages during this infection. This was confirmed by addition of these mediators to the culture medium before infection; PAF (10 -6, 10 -9 and 10-1Z M) reduced significantly the infection whereas PGEz (10-M) induced a marked enhancement. This effect of exogenous PAF on macrophage infection was reversed by the two PAF antagonists used in this study as well as by the inhibitor of nitric oxide synthesis, L-arginine methyl ester (100 mM). Taken together the data suggest that endogenous production of PAF and PGE2 exert opposing effects on Lesbmana-macrophage interaction and that nitric oxide may be involved in the augmented destruction of parasites induced by PAF.

Essential Role of Platelet-Activating Factor in Control ofLeishmania(Leishmania)amazonensisInfection

“…PGE 2 decreases macrophage leishmanicidal activity. In a previous study we showed that the addition of PGE 2 to resident macrophages obtained from susceptible BALB/c mice induced a significant increase in the infection index (25). Here we confirmed this effect of PGE 2 in TG-elicited macrophages of C57BL/6 mice.…”

“…We have previously shown that the addition of PGE 2 to resident BALB/c macrophages strongly reduced their leishmanicidal capacity (25). In the present study we confirmed this observation in TG-elicited macrophages obtained from C57BL/6 mice.…”

“…We have shown that prostaglandins, either endogenously produced or added to the macrophage cultures, enhance Leishmania (Leishmania) amazonensis growth in resident murine (BALB/c) macrophages. Moreover, we provided the first evidence that PAF modulates macrophage leishmanicidal activity, causing a marked decrease of the in vitro infection (25). This effect of PAF appeared to be mediated by an NO-dependent mechanism, since the addition of NO inhibitors reverted the protective effect of PAF.…”

“…This effect of PAF appeared to be mediated by an NO-dependent mechanism, since the addition of NO inhibitors reverted the protective effect of PAF. However, NO was not detected in these cultures (25). In the present study, we further examined the relationship between lipid mediators, NO production, and the leishmanicidal activity of macrophages.…”

Platelet-Activating Factor Receptor Contributes to Antileishmanial Function of Miltefosine

“…Although PAF enhanced killing of L. amazonensis, some of its antagonists inhibited the parasite clearance in mouse macrophages (13)(14)(15). Accordingly, PAF receptor (PAF receptor) is perhaps the most feasible candidate to serve as an HPC receptor.…”