Pathophysiological effects of antibodies against Trypanosoma cruzi ribosomal P proteins in cardiac cells.

L TASSO; G LEVY; L SIMONETTI; A BENATAR; MJ LEVIN; KA GOMEZ

La Plata, Buenos Aires

Encuentro; XVIII Meeting ISHR Latin American Section; 2010

International Society for Heart Research, Latin American Section

High levels of antibodies (Abs) against the C-terminal end of the Trypanosoma cruzi (T. cruzi) ribosomal P2beta protein, defined by the R13 peptide, are detected in sera of patients with chronic Chagas heart disease (cChHD). In previous works, we demonstrated that these Abs also recognize an epitope on the second extracellular loop of the Beta1-adrenergic receptor (B1-AR), inducing a functional response on cardiomyocytes. Here, we show that a monoclonal Ab against the R13 peptide, called mAb 17.2 and its single chain Fv fragment (svFc) C5, provoked apoptosis in murine HL-1 cardiac cells, through the beta-adrenergic pathway. The Abs apoptotic effect might be mediated via the mitochondrial intrinsic pathway since an increase in mRNA levels was evidenced. Interestingly, another svFc anti-P2b protein, acting as B1-AR antagonist, protected cells from apoptosis induced by svFc C5. In addition, HL-1 also underwent apoptotic cell death after incubation with IgGs from patients with cChHD (39.1%) that presented reactivity against R13 peptide. This effect was partially abolished by preincubation with R13 peptide or propranolol, suggesting the involvement of the C-terminal end of ribosomal P proteins and also the beta-adrenergic pathway. Our findings strongly demonstrate that anti-R13 Abs generated during the chronic infection by T.cruzi have a strong cardiomyocyte apoptosis inducing ability, which could contribute to the heart disease developed in patients with cChHD.