Papel dos receptores B1 e B2 de bradicinina e de captopril nas interações célula hospedeira-Trypanosoma cruzi

AUTOR(ES)

Janete Soares Coelho dos Santos

FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

27/08/2010

RESUMO

The infection of monocytes by Trypanosoma cruzi tripomastigotes is a crucial step for the development of Chagas disease immune response. Infection by T. cruzi has demonstrated to be an active process, involving diverse cellular components and different cell types. Previous studies of the interaction tissue-culture derived trypomastigotes (TCT) between cardiomyocytes or endothelial cells appointed the bradykinin receptors (B2 or B1 subtype) as transducers of Ca2+-dependent responses leading to cellular invasion. Generation of the kinin agonist, presumably occurring in host-parasite synapses, is thought to depend on cruzipain-mediated processing of cell-bound kininogens. Once released, kinins either bind to their cognate G-protein coupled receptors, or are swiftly degraded by metallopeptidases, such as the angiotensin-converting enzyme (ACE). Studies show that these receptors are also involved in activation and modulation of immune cells through the production or inhibition of cytokines. Here we checked if addition of ACE inhibitor (captopril) and/or antagonists of the kinin receptors could influence the outcome of TCT (Y strain) interaction with human monocytes. We also evaluated whether these antagonists and captopril may influence the expression of important molecules to activation and effector function of monocytes CD14+ and CD4+ and CD8+ lymphocytes. These parameters were analyzed in cells from non-chagasic individuals, as well as cells from patients with indeterminate or cardiac clinical forms of Chagas disease. Our results showed that treatment with either B2 or B1 antagonists reduces the frequency of monocytes infected with T. cruzi. Interestingly, while captopril does not alter the percentage of infected cells, it increases the extent of parasite infectivity on a cell-per cell basis, while inducing a decrease in IL-10 expression. These data point to the need of better studing the effects of captopril in the immune response of Chagas patients, considering that this drug is often prescribed to hypertensive chagasic patients. Furthermore, changes were seen in the expression of molecules by monocytes pre-treated with captopril and specific B2 or B1 antagonist and infected by T. cruzi. However, the modulation of these molecules did not follow the same pattern in different groups. Ours results showed that the pathway of kinins and captopril can act in the process of activation of CD4+ T cells, leading to the expression of IL-17 by these cells. In conclusion, this work shows that parasite uptake by monocytes is partially dependent on kinin receptor signaling. Moreover, captopril and kinin receptor signaling may be important in the immune response against the stimulation with the parasite T. cruzi

ASSUNTO(S)

biologia celular teses. tripanossoma cruzi teses. monócitos teses. bradicinina teses. captopril decs

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