Sterin-Borda L J, Borda E S
Centro de Estudios Farmacológicos y de Botánica (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Acta Physiol Pharmacol Ther Latinoam. 1994;44(4):109-23.
Evidences accumulated over the last decade give adequate proof for the existence of circulating antibodies in Chagas disease which binds to beta adrenergic and muscarinic cholinergic receptor of lymphocytes and myocardium. The interaction of the antibodies with lymphocytes and cardiac neurotransmitter receptors behaving as an agonist, triggers in the cells intracellular signal transductions that alter the physiological behaviour of this cells. These events converted the cells in pathologically active cells. Thus, antibodies activating beta adrenergic receptors of T helper (Th) lymphocytes increase cAMP and releases PGE2 by T suppressor/cytotoxic (Ts/c) cell, inducing in this way, immunosuppression by simultaneous inhibition of Th and stimulation of Ts/c cell function. All these antibodies actions were mimetized by parasite's membranes. On the other hand, the interaction of antibodies against heart beta adrenergic and cholinergic receptors trigger physiologic, morphologic, enzymatic and molecular alterations, that leading to cardiac damage. The analysis of the prevalence and distribution of these antibodies shows a strong association with seropositive asymptomatic patients with autonomic dysfunction in comparison with those asymptomatic without alteration of the heart autonomic disorders; pointing to that the presence of these antibodies may partially explain the cardiomyoneuropathy of Chagas disease, in which the sympathetic and parasympathetic systems are affected. The deposit of autoantibodies on the myocardial neurotransmitter receptors, behaving like an agonist, could induced desensitization and/or down regulation of the receptors. This in turn, could led to a progressive blockade of myocardium neurotransmitter receptors, with sympathetic and parasympathetic dennervation, a phenomenon that has been described in the course of Chagas cardioneuropathy.
过去十年积累的证据充分证明，恰加斯病（南美锥虫病）存在循环抗体，这些抗体可与淋巴细胞和心肌的β-肾上腺素能及毒蕈碱胆碱能受体结合。抗体与淋巴细胞及心脏神经递质受体相互作用，表现为激动剂，触发细胞内信号转导，改变这些细胞的生理行为。这些事件使细胞转变为病理活性细胞。因此，激活辅助性T（Th）淋巴细胞β-肾上腺素能受体的抗体增加环磷酸腺苷（cAMP），并通过抑制性/细胞毒性T（Ts/c）细胞释放前列腺素E2，从而通过同时抑制Th和刺激Ts/c细胞功能诱导免疫抑制。寄生虫膜可模拟所有这些抗体的作用。另一方面，针对心脏β-肾上腺素能和胆碱能受体的抗体相互作用引发生理、形态、酶学和分子改变，导致心脏损伤。对这些抗体的患病率和分布分析表明，与无心脏自主神经功能紊乱改变的无症状患者相比，血清学阳性的自主神经功能障碍无症状患者与之有很强的关联；这表明这些抗体的存在可能部分解释了恰加斯病的心肌神经病变，其中交感和副交感神经系统均受影响。自身抗体沉积在心肌神经递质受体上，表现为激动剂，可诱导受体脱敏和/或下调。这反过来可能导致心肌神经递质受体的逐渐阻断，伴有交感和副交感神经去神经支配，这一现象在恰加斯病心肌神经病变过程中已有描述。
