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

Encuentro; XVIII Meeting ISHR Latin American Section; 2010

High levels of antibodies (Abs) against the C-terminal end of the Trypanosoma cruzi (T. cruzi) ribosomal P2b protein, defined by the R13 peptide, are detected in sera from patients with chronic Chagas Heart Disease (cChHD). In previous works, we have demonstrated that these Abs also recognize an epitope on the second extracellular loop of the b1-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 â-adrenergic pathway. The 17.2 apoptotic effect  might be mediated via the mitochondrial intrinsic pathway since an increase in Bax/BclXL 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 9 of 23 IgGs from patients with cChHD (39.1%) that presented reactivity against R13 peptide and b1-AR. This effect was partially abolished by preincubation with R13 peptide or propranolol, suggesting the involvement of the anti-R13 epitope and also the â-adrenergic pathway. Our findings 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.