INVESTIGADORES
LONGHI silvia andrea
artículos
Título:
Antibodies against the Trypanosoma cruzi ribosomal P proteins induce apoptosis in HL-1 cardiac cells.
Autor/es:
LEVY G; TASSO LM; LONGHI SA; GARCIA RIVELLO H ; KYTO V; SAUKKO P; LEVIN MJ; GOMEZ KA
Revista:
INTERNATIONAL JOURNAL FOR PARASITOLOGY
Editorial:
ELSEVIER SCI LTD
Referencias:
Lugar: Oxford; Año: 2011 vol. 41 p. 635 - 644
ISSN:
0020-7519
Resumen:
High levels of antibodies (Abs) against the C-terminal end of the Trypanosoma cruzi ribosomal P2b 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 b1-adrenergic receptor (b1-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 b-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, BclXL, 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 b1-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 b-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.