Antibodies against the Trypanosoma cruzi ribosomal P proteins induce apoptosis in HL-1 cardiac cells

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• 作者：Gabriela V. Levy^a ; ¹ ; Laura M. Tasso^a ; Silvia A. Longhi^a ; Herná ; n Garcí ; a Rivello^b ; Ville Kytö ; ^c ; Pekka Saukko^d ; Mariano J. Levin^a ; Karina A. Gó ; mez^a ; ^{gomez@dna.uba.ar"" rel=""nofollow}
• 关键词：Trypanosoma cruzi ; Chronic Chagas heart disease ; β ; -Adrenergic receptor ; Anti-ribosomal P proteins antibodies ; Apoptosis ; Cardiomyocytes
• 刊名：International Journal for Parasitology
• 出版年：2011
• 出版时间：May 2011
• 年：2011
• 卷：41
• 期：6
• 页码：635-644
• 全文大小：1161 K

文摘

High levels of antibodies (Abs) against the C-terminal end of the Trypanosoma cruzi ribosomal P2β protein, defined by the R13 peptide, are detected in sera from patients with chronic Chagas heart disease (cChHD). These Abs can cross-react with the β1-adrenergic receptor (β1-AR), inducing a functional response in cardiomyocytes. In this study, we report that a monoclonal Ab against the R13 peptide, called mAb 17.2, and its single-chain Fv fragment (scFv), C5, caused apoptosis of murine adult cardiac HL-1 cells, and this effect was inhibited by pre-incubation with the β-blocker, propranolol. In addition, apoptosis induced by mAb 17.2 might involve the mitochondrial pathway evidenced by an increase in pro-apoptotic molecule, Bax/anti-apoptotic molecule, Bcl_XL, mRNA levels. HL-1 cells also underwent apoptosis after incubation with nine of 23 IgGs from cChHD patients (39.1 % ) that presented reactivity against R13 peptide and β1-AR. The apoptotic effect caused by these IgGs was partially abolished by pre-incubation with R13 peptide or propranolol, suggesting the involvement of the C-terminal end of ribosomal P proteins and the β-adrenergic pathway. Moreover, we observed high rates of cardiomyocyte apoptosis in two tissue samples from cChHD patients by using a TUNEL assay and staining of active caspase-3. Our data demonstrate that Abs developed during T. cruzi infection have a strong cardiomyocyte apoptosis inducing ability, which could contribute to the heart disease developed in patients with cChHD.