Mast cells and eosinophils are the key effector cells of allergic disorders. Although most studies on eosinophilic esophagitis (EoE), an allergic disorder of the esophagus, have focused on the role of eosinophils, recent studies suggest a major role for mast cells in causing the clinical manifestations of this disease. Cellular and animal studies have demonstrated that mast cells can cause esophageal muscle cells to proliferate and differentiate into a more contractile phenotype, and that mediators released by degranulating mast cells such as tryptase and histamine can activate smooth muscle contraction pathways. Thus, activated mast cells in the esophageal muscularis propria might cause esophageal motility abnormalities, including the failure of lower esophageal sphincter relaxation typical of achalasia. In addition, mast cells have been implicated in the pathogenesis of a number of neurodegenerative disorders of the central nervous system such as Alzheimer's and Parkinson's diseases, because degranulating mast cells release pro-inflammatory and cytotoxic mediators capable of damaging neurons. Such mast cell degranulation in the myenteric plexus of the esophagus could cause the loss of enteric neurons that characterizes achalasia. In this report, we review the molecular mechanisms of esophageal smooth muscle contraction, and how mast cells products might affect that muscle and cause neurodegeneration in the esophagus. Based on these data, we present our novel, conceptual model for an allergy-induced form of achalasia mediated by mast cell activation in the esophageal muscularis propria.

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肥大细胞对食管平滑肌的影响及其在嗜酸性食管炎和口疮中的潜在作用

肥大细胞和嗜酸性粒细胞是过敏性疾病的关键效应细胞。尽管大多数关于嗜酸性粒细胞性食管炎（EoE）（一种食道过敏性疾病）的研究都集中在嗜酸性粒细胞的作用上，但最近的研究表明肥大细胞在引起该疾病的临床表现中起主要作用。细胞和动物研究表明，肥大细胞可引起食管肌细胞增殖并分化为更具收缩性的表型，而脱粒肥大细胞释放的介体如类胰蛋白酶和组胺可激活平滑肌收缩途径。因此，食管固有肌中肥大细胞的活化可能引起食管运动异常，包括including门失弛缓性食管下括约肌松弛的失败。此外，肥大细胞与许多中枢神经系统神经退行性疾病（例如阿尔茨海默氏病和帕金森氏病）的发病机制有关，因为脱粒的肥大细胞释放出能够破坏神经元的促炎性和细胞毒性介质。食管的肌层神经丛中的这种肥大细胞脱粒可引起表征门失弛缓症的肠神经元的损失。在本报告中，我们回顾了食管平滑肌收缩的分子机制，以及肥大细胞产物如何影响该肌肉并引起食道神经变性。基于这些数据，我们提出了由食管性固有肌肥大细胞激活介导的变应性失弛缓症形式的新颖概念模型。