Glycoinositolphospholipids of Leishmania major inhibit nitric oxide synthesis and reduce leishmanicidal activity in murine macrophages

Abstract

Murine macrophages express high levels of inducible nitric oxide (NO) synthase and produce large amounts of nitric oxide when activated with interferon-gamma and lipopolysaccharide in vitro. Nitric oxide is a mediator of a variety of biological functions including microbicidal activity against the protozoan parasite Leishmania species. Glycoinositolphospholipids (GIPL) are the predominant surface glycolipids in both developmental stages of Leishmania major. We report here that GIPL can inhibit the synthesis of NO in a time- and dose-dependent manner. In contrast, lipophosphoglycan, which is present in the promastigote stage did not inhibit NO synthesis. GIPL-treated macrophages also showed markedly reduced leishmanicidal activity. The majority of the inhibitory activity of GIPL was found within the alkylacylglycerol moiety of the GIPL molecule. These data, therefore, suggest that GIPL may contribute towards the survival of the parasite in the immune hosts.