Participation of molecule Fas-L in the acute myocarditis promoted by the experimental infection for the Trypanosoma cruzi: cellular inflammatory regulation and evolution of the cardiac insufficiency.

by de Oliveira, Gabriel Melo

Abstract (Summary)
The Fas-L molecule is classically associated with apoptosis and cellular death. However, it is also known that this molecule is involved in various regulatory mechanisms of acquired immune and inflammatory responses, through cellular activation and secretion of quimiotactic factors, for example. In addition, this molecule is also apparently involved in a systemic regulation of cardiac and renal function. This work aims to study theimportance of Fas/Fas-L interaction in the inflammatory regulation of acute myocarditis and in the progression of cardiac insufficiency in mice infected with Trypanosoma cruzi.Our results using Fas-L deficient mice showed a moderate acute myocarditis and, accordingly, reduction in cardiomyocytes death. However, there was a high mortality ratewhen compared with BALB/c mice. We observed through flow cytometry that in the absence of Fas-L there are mostly CD4+ T cells in the cardiac tissue and a Th1/Th2 response. Differently from the wild type infected mice, which have predominantly CD8+ T and a Th1 biased response. We further studied the cause of death of deficient mice and observed a more pronounced and earlier cardiac and renal dysfunction possibly related to death. Moreover, there were additional alterations in arterial pressure, cardiac electric conduction and hematological evaluation of both mice lineages. We concluded that the Fas-L molecule is not directly involved in cardiomyocytes destruction, but acts locally regulating the equilibrium and profile of cytokines and cellular inflammatory infiltration.Additionally, Fas-L acts systemically promoting a fulminant cardiac insufficiency through a cardio-anemic-renal syndrome.
This document abstract is also available in Portuguese.
Bibliographical Information:

Advisor:Tania Cremonini de Araújo-Jorge; Andréa Henriques-Pons

School:Faculdades Oswaldo Cruz

School Location:Brazil

Source Type:Master's Thesis

Keywords:Trypanosoma cruzi Cell Death Chagas Cardiomyopathy Flow Cytometry


Date of Publication:12/10/2007

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