Trypanosoma cruzi antigen that interacts with the b1-adrenergic receptor and modifies myocardial contractile activity

JOENSEN, LG; BORDA, E; KOHOUT, T; PERRY, S; GARCIA, GA; STERIN-BORDA, L

MOLECULAR AND BIOCHEMICAL PARASITOLOGY

Año: 2003 vol. 127 p. 169 - 177

0166-6851

Previously, we have demonstrated that plasma membranes from the parasite Trypanosoma cruzi (T. cruzi) recognize and adhere to host cells through parasite surface attachment molecules that have affinity for b1-adrenergic receptors (b1-ARs) on target organs. In this report we identify a parasite protein that not only interacts with b1-ARs, but also displays b-agonist-like activity. We demonstrate that a recombinant maltose binding protein fusion of Tc13Tul (MBP-Tc13Tul), a member of the T. cruzi antigen 13 family of surface antigen proteins, competes for binding sites with the b-adrenergic receptor antagonist [ 125 I]-CYP on membranes purified both from CHO cells expressing human b1-ARs and from rat atria. The competition is prevented by pre-treating MBP-Tc13Tul with antibodies directed against the EPKSA repeat domain of Tc13Tul, implicating this portion of the molecule in binding to the b1-AR. Furthermore, MBP-Tc13Tul activates rat myocardial b1-ARs, resulting in synthesis of cyclic adenosine monophosphate (cAMP) and an increase in cardiac contractility. These biological effects are selectively suppressed by the b1-AR antagonist atenolol, by a synthetic peptide corresponding to the second extracellular loop of the human b1-AR, and by the anti-EPKSA repeat antibodies. These results imply that the Tc13Tul cell-surface antigen of T. cruzi plays a central role in misregulating the b1-AR following parasite infection, and may be a causative factor of dysautonomic syndrome described in Chagas’ disease.