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

Abstract

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.

• Authors: Gabriela V Levy, Laura M Tasso, Silvia A Longhi, Hernán García Rivello, Ville Kytö, Pekka Saukko, Mariano J Levin, Karina A Gómez
• Journal: International journal for parasitology (Int J Parasitol) Vol. 41 Issue 6 Pg. 635-44 (May 2011) ISSN: 1879-0135 [Electronic] England
• PMID: 21255576 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Protozoan
• Antigens, Protozoan
• Phosphoproteins
• Receptors, Adrenergic, beta
• Ribosomal Proteins
• Single-Chain Antibodies
• phosphoprotein P2, ribosomal
• Caspase 3

Topics

• Animals
• Antibodies, Monoclonal (immunology)
• Antibodies, Protozoan (immunology)
• Antigens, Protozoan (immunology)
• Apoptosis
• Caspase 3 (metabolism)
• Cell Line
• Cross Reactions
• Female
• Humans
• In Situ Nick-End Labeling
• Male
• Mice
• Middle Aged
• Myocytes, Cardiac (physiology)
• Phosphoproteins (immunology)
• Receptors, Adrenergic, beta (immunology)
• Ribosomal Proteins (immunology)
• Single-Chain Antibodies (immunology)
• Trypanosoma cruzi (immunology)