INGEBI   02650
INSTITUTO DE INVESTIGACIONES EN INGENIERIA GENETICA Y BIOLOGIA MOLECULAR "DR. HECTOR N TORRES"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Antibodies against Trypanosoma cruzi ribosomal P proteins induce apoptosis on HL-1 cardiac cells
Autor/es:
LEVY, GV; TASSO, LM; LEVIN MJ; GÓMEZ KA
Lugar:
Águas de Lindóa, SP, Brasil
Reunión:
Congreso; XXXV Annual Meeting on Basic Research in Chagas´ Disease – XXIV Annual Meeting of the Brazilian Society of Protozoology; 2008
Resumen:
Chronic Chagas Heart Disease (cChHD) is characterized by high antibody (Ab) levels mainly toward parasite intracellular proteins. Among these, the acidic C-terminal region of the ribosomal P proteins (epitope R13 of TcP2b protein) is considered to be highly immunogenic and bears similarity with the second extracellular loop of the b1-adrenergic receptor (b1-AR). Our previous results demonstrated that anti-R13 Abs from patients with cChHD recognize and activate b1-AR and M2-cholinergic receptors (M2-ChR), as seen by immunocytochemistry and cAMP accumulation on stably transfected cells. The aim of this work was to evaluate the effect of anti-R13 Abs long-term stimulation on cardiac cells. Thus, adult murine cardiac HL-1 cells were treated with the adrenergic agonist Isoproterenol (ISO), mAb anti-R13, named 17.2, or IgG fractions from cChHD patients. The results showed that ISO produced cell cycle arrest, cellular senescence and apoptosis and mAb 17.2 induced apoptosis by b-AR stimulation on cardiac HL-1 cells as seen by TUNEL. Moreover, mAb 17.2 produced an increase in Bax/BclXL ratio mRNA levels. Late apoptosis changes on cardiac cells induced by mAb 17.2 were further confirmed using annexin V-PI dual staining by flow cytometry. Likewise, IgG fractions from cChHD patients produced apoptosis on these cells when compared to IgGs from healthy individuals. These results support the hypothesis that apoptosis caused by anti-R13 Ab chronic stimulation on b1-adrenergic receptors could result in cardiotoxic effects similar to those known to be produced by long term exposure to agonists. This may justify the use of immunoadsorption approaches to avoid the cross-reactive immune response produced by anti-R13 Abs without interfering with anti-parasite immunity. This research was supported by grants from The National Agency of Scientific and Technological Promotion (FONCYT BID 1728/OC-AR 01-14389 and 25845).