Modulation of cardiac physiology by an anti-Trypanosoma cruzi monoclonal antibody after interaction with myocardium.
Circulating antibodies from human and murine chagasic sera are able to interact with myocardium, activating neurotransmitter receptors. Here, we studied the effects of a monoclonal antibody (MAb CAK20.12), which recognizes a 150 kilodalton antigen of Trypanosoma cruzi and reacts with normal human and murine striated muscles and with cardiac tissue. The MAb CAK20.12 binds to purified cardiac membranes and interferes with the binding of beta-adrenergic receptor radioligand ([125I]CYP) and muscarinic cholinergic receptor (mAChR) radioligand ([3H]QNB) in a noncompetitive way. As a consequence of this interaction, beta-adrenergic receptor and mAChR were activated, leading to increased intracellular levels of cyclic AMP as a result of beta-adrenergic receptor-coupled adenylate cyclase triggering. When its sympathetic action was abrogated, it also induced an mAChR-mediated increase in cyclic GMP. Furthermore, cardiac physiology was modified by MAb CAK20.12, as it was able to increase cardiac contractility through beta-adrenoceptor activation and to decrease atrial frequency as a result of mAChR activation. The fact that this MAb modulates and modifies the mechanical and biochemical activity of normal murine heart established an important basis for future research and understanding of how the host's humoral immune response acts on the course and development of the chronic chagasic myocardiopathy.
Cremaschi
G
G
Centro de Estudios Farmacológicos y Botánicos (CEFYBO-CONICET), Buenos Aires, Argentina.
Zwirner
N W
NW
Gorelik
G
G
Malchiodi
E L
EL
Chiaramonte
M G
MG
Fossati
C A
CA
Sterin-Borda
L
L
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000913:Antibodies, Protozoan / Q000276:immunology*; D002598:Chagas Cardiomyopathy / Q000276:immunology / Q000503:physiopathology*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D006321:Heart / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D020120:Iodocyanopindolol; D051379:Mice; D008807:Mice, Inbred BALB C; D018727:Muscarinic Antagonists / Q000378:metabolism; D009200:Myocardial Contraction; D009206:Myocardium / Q000276:immunology / Q000378:metabolism; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000913:Antibodies, Protozoan; D018727:Muscarinic Antagonists; D011813:Quinuclidinyl Benzilate; D020120:Iodocyanopindolol; D010869:Pindolol; D000242:Cyclic AMP; D006152:Cyclic GMP