Antibodies against the Trypanosoma cruzi ribosomal P proteins induce apoptosis in HL-1 cardiac cells.
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.
Instituto de Investigaciones en Ingeniería Genética y Biología Molecular (INGEBI-CONICET), Buenos Aires, Argentina.
Gabriela V
GV
Levy
Laura M
LM
Tasso
Silvia A
SA
Longhi
Hernán García
HG
Rivello
Ville
V
Kytö
Pekka
P
Saukko
Mariano J
MJ
Levin
Karina A
KA
Gómez
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000913:Antibodies, Protozoan / Q000276:immunology*; D000953:Antigens, Protozoan / Q000276:immunology*; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D003429:Cross Reactions; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000502:physiology*; D010750:Phosphoproteins / Q000276:immunology*; D011943:Receptors, Adrenergic, beta / Q000276:immunology; D012269:Ribosomal Proteins / Q000276:immunology*; D057127:Single-Chain Antibodies / Q000276:immunology; D014349:Trypanosoma cruzi / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D010750:Phosphoproteins; D011943:Receptors, Adrenergic, beta; D012269:Ribosomal Proteins; D057127:Single-Chain Antibodies; C031937:phosphoprotein P2, ribosomal; D053148:Caspase 3