INGEBI   02650
INSTITUTO DE INVESTIGACIONES EN INGENIERIA GENETICA Y BIOLOGIA MOLECULAR "DR. HECTOR N TORRES"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Pathophysiological effects of antibodies against Trypanosoma cruzi ribosomal P proteins in cardiac cells
Autor/es:
TASSO, LAURA M; LEVY, GABRIELA V; SIMONETTI, LEANDRO; BENATAR, ALEJANDRO; LEVIN, MARIANO J; GÓMEZ, KARINA A
Lugar:
Hospital Universitario Integrado - Facultad de Cs. Médicas de La Plat
Reunión:
Jornada; XVIII Reunión anual de la ISHR; 2010
Institución organizadora:
Sección Latino Americana de la ISHR
Resumen:
High levels of antibodies (Abs) against the C-terminal end of the Trypanosoma cruzi (T. cruzi) ribosomal P2β 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 β1-adrenergic receptor (β1-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 β-adrenergic pathway. The Abs apoptotic effect might be mediated via the mitochondrial intrinsic pathway since an increase in Bax/BclXL mRNA levels was evidenced. Interestingly, another svFc anti- P2β protein, acting as β1-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 β1-AR. 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 β-adrenergic pathway. Our findings strongly demonstrate that anti-R13 Abs generated during the chronic infection by T.cruzihave a strong cardiomyocyte apoptosis inducing ability, which could contribute to the heart disease developed in patients with cChHD.