Participation of nitric oxide signalling system in the cardiac muscarinic cholinergic effect of human chagasic IgG

STERIN-BORDA, L.; VILA ECHAGÜE, A.; GOIN, J.C.; PÉREZ LEIRÓS, C.; GENARO, A.; CREMASCHI, G.; BORDA, E.

Zacatecas, México

Congreso; IV Latin American Congress of Immunology and XII Mexican Congress of Immunology; 1996

Asociación Latinoamericana de Inmunología y Sociedad Mexicana de Inmunología

The possible role of altered humoral immune response in the chronic chagasic cardioneuromyopathy was examined by analyzing the interaction of IgG from T. cruzi infected patients with cardiac muscarinic cholinergic receptors (mAchR). Human chagasic IgG activating M2 mAChR simulated the agonist actions, exerting negative inotropic effect, activation of phosphoinositide turnover, PKC activity, stimulation of nitric oxide synthase (NOS) and increased production of cGMP. Inhibitors of phospholipase C, protein kinase C, calcium-calmodulin, NOS and guanilate cyclase activities prevented the chagasic IgG modification of intracellular events associated with specific receptor activation. In addition, sodium nitroprusside, isosorbide and 8-bromo cyclic GMP mimicked the chagasic IgG effect associated with cholinergic-mediated cellular transmembrane signals. Moreover, this chagasic IgG immunoprecipitated the mAchRs solubilized from cardiac membranes. In SDS-PAGE and immunoblotting analysis, chagasic sera recognized a band of 70-75 kDa, an apparent molecular weight similar to that of the mAChRs, which disappeared with atropine. It is possible that the  chronic interaction of chagasic IgG with myocardial mAChR, behaving as a muscarinic agonist and inducing release of nitric oxide, leads to the cell dysfunction or tissue damage.