Role of kinins during experimental Plasmodium infection

Abstract

Malaria is a serious public health problem that has severe socio-economical consequences, since the disease and poverty are strictly correlated. According to the World Health Organization, 30% of the world population lives in endemic areas of the disease. The etiologic agent of malaria is a protozoan of the genus Plasmodium and its life cycle involves a vertebrate and an invertebrate hosts. The invertebrate host is the mosquito Anopheles that transmits different infecting species. In the vertebrate host, the intra-erythrocytic cycle is responsible for the clinical manifestation of the disease, such as periodic fevers, severe anemia and imbalance of inflammatory system, in coagulation process and in hemodynamic.Previous studies from our group have shown that Plasmodium is capable to process plasma proteins, as plasminogen and kininogen, generating kinins and angiostatin, respectively. Kinins, in particular bradykinin, have a vasodilator, antiproliferative, antifibrotic, anti-thrombotic effect. Bradykinin is also associated with the release of endothelial factors such as nitric oxide, prostaglandins and tissue plasminogen activator.Taken together, the aim of this project is to study the participation of kinins in the pathophysiology of malaria in wild type and knockout mice for the bradykinin receptors, infected with different strains of Plasmodium such as P. chabaudi AS, P. chabaudi AJ and P. berguei ANKA. In these models will be determined the nitric oxide and bradykinin concentrations, hematological changes, coagulation factors and the inflammatory cytokines profile. It will also be evaluated the gene and protein expression of bradykinin receptors.In human malaria, the action of kinins generated by the hydrolysis of kininogen, will be evaluated in P. falciparum cellular events such as proliferation, adhesion, migration and viability, and also possible changes in cytoadherence.