Structural and functional analysis of a platelet-activating lysophosphatidylcholine of Trypanosoma cruzi.

摘要: Background Trypanosoma cruzi is the causative agent of life-threatening Chagas disease, in which increased platelet aggregation related to myocarditis observed. Platelet-activating factor (PAF) a potent intercellular lipid mediator and second messenger that exerts its activity through PAF-specific receptor (PAFR). Previous data from our group suggested T. synthesizes phospholipid with PAF-like activity. The structure molecule, however, remains elusive. Methodology/Principal findings Here, we have purified structurally characterized putative molecule by electrospray ionization-tandem mass spectrometry (ESI-MS/MS). Our ESI-MS/MS demonstrated actually lysophosphatidylcholine (LPC), namely sn-1 C18:1(delta 9)-LPC. Similar PAF, platelet-aggregating C18:1-LPC was abrogated PAFR antagonist, WEB 2086. Other major LPC species, i.e., C16:0-, C18:0-, C18:2-LPC, were also all stages. These failed induce aggregation. Quantification species ESI-MS revealed intracellular amastigote trypomastigote forms much higher levels than epimastigote metacyclic forms. found be secreted parasite extracellular vesicles (EV) an EV-free fraction. A three-dimensional model constructed molecular docking study performed predict interactions between each species. Molecular that, contrary other analyzed, predicted interact fashion similar PAF. Conclusions/Significance Taken together, indicate bioactive C18:1-LPC, aggregates platelets via PAFR. We propose might important progression disease biosynthesis could eventually exploited as potential target for new therapeutic interventions.