PHOSPHOLIPASE A1 AND LIPIDS FROM LEISHMANIA BRAZILIENSIS. ITS POSSIBLE PARTICIPATION IN THE PATHOGENESIS OF LEISHMANIASIS

BELAUNZARÁN ML; GIMENEZ G; BOTT E; LAMMEL EM; ISOLA ELD

Porto de Galinhas, Pernambuco.

Congreso; Fifth World Congress on Leishmaniasis; 2013

Leishmania spp, an intracellular parasite that belongs to the Trypanosomatidae family is transmitted by phlebotomine sandflies as metacyclic promastigotes that infect macrophages in the vertebrate host, where they multiply as amastigotes. In Argentina, the coexistence of L. braziliensis, L. guyanensis and L. amazonensis has been detected, being the major causative agents of human leishmaniasis.Phospholipase A1 (PLA1) specifically hydrolyses acyl groups from phospholiplids (PL) at the sn-1 position and is considered a virulence factor for many pathogens, trypanosomatids among them. On the other hand, the limitation of initial infection depends on the activation of the innate immunity and there is a growing body of evidence pointing to an important modulatory role of microorganisms' lipids in this process. In this regard, we have previously reported in T. cruzi a rapid accumulation of free fatty acids (FFA) and lysophospholipids upon parasite autolysis, as result of PLA1 activity. These compounds function as second messengers and have been implicated in inflammatory processes. As we previously demonstrated that L. braziliensis also possesses this enzymatic activity, in the present work we performed its biochemical characterization and analyzed the lipid profiles of autolysing parasites as well as the effect of these lipids in nitric oxide release from macrophages.Results indicated that in amastigotes and promastigotes PLA1 activity was mainly associated to the soluble fractions. Interestingly, the activity levels were significantly high in the infective amastigotes, being in the soluble and in the organelle enriched fractions 2- and 8-fold higher respectively, compared to non-infective promastigotes. In both stages, PLA1 activity was independent of the bivalent cations Ca2+ and Mg2+, with an optimum pH of 6.3 and only for amastigotes, the enzyme was activated by Triton X-100. On the other hand, the lipid analysis of autolysing amastigotes showed a significant PL degradation with an important increase in FFA, indicating the action of parasite PLA1. Moreover, total lipids from these parasites were able to induce in macrophages nitric oxide release, a soluble factor implicated in parasite growth inhibition.In conclusion, PL degradation in autolysing amastigotes due to parasite PLA1 activity generated FFA, second lipid messenger that could participate in several signaling pathways related to inflammatory processes in Leishmaniasis.Supported by FONCYT/CONICET