Mast cells infiltrate the esophageal smooth muscle in patients with eosinophilic esophagitis, express TGF-β1, and increase esophageal smooth muscle contraction
Mast cells infiltrate the esophageal smooth muscle in patients with eosinophilic esophagitis, express TGF-β1, and increase esophageal smooth muscle contraction
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DOI：
10.1016/j.jaci.2010.08.050
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发表时间：
2010-12-01
影响因子：
14.2
通讯作者：
Broide, David H.
中科院分区：
文献类型：
--
作者：
Aceves, Seema S.;Chen, Diana;Broide, David H.
背景：嗜酸性食管炎(EE)患者的食道上皮中肥大细胞数量增加。目的：研究肥大细胞在食道固有层(LP)和平滑肌(SM)中的定位和特征，肥大细胞转化生长因子-β1表达对体外培养的人食管平滑肌(HESM)细胞收缩的功能意义，以及外用糖皮质激素对EE患者肥大细胞类胰蛋白酶(MCT)阳性(MCT)和糜酶(MCC)阳性细胞数量的影响。方法：对EE患者上皮、外用糖皮质激素治疗前后LP中MCT和MCC阳性的肥大细胞进行定量。并用免疫组织化学方法对EE患者和对照组的粘膜肌层进行了观察。采用双重免疫荧光法检测肥大细胞产生的转化生长因子-β1，并在体外检测转化生长因子-β1对HESM细胞收缩功能的影响。结果：在EE患者的SM中，MCT-和TGF-β1阳性的细胞数显著高于对照组(但仅有少量的嗜酸性粒细胞)。MCT表达转化生长因子-β1，可增强体外培养的原代Hesm细胞的收缩能力。结论：EE患者SM中MCT数量增加，而不是嗜酸性粒细胞数量增加，表达转化生长因子-β1，并增加体外培养的Hesm细胞的收缩能力。因此，在EE患者中，肥大细胞定位于SM可能调节食道收缩。(《过敏与免疫杂志》2010；126：1198-204。)
Background: Increased numbers of mast cells are present in the esophageal epithelium in patients with eosinophilic esophagitis (EE). However, mast cell infiltration into the esophageal lamina propria (LP) and smooth muscle (SM) and the effects of their products on SM function has not been determined.Objective: We investigated mast cell localization and characterization in esophageal SM, the functional significance of mast cell TGF-beta 1 expression to contraction of human esophageal smooth muscle (HESM) cells in vitro, and the effect of topical corticosteroids on the number of tryptase-positive (MCT) and chymase-positive (MCC) mast cells in patients with EE.Methods: MCT- and MCC-positive mast cell numbers were quantitated in the epithelium, the LP before and after topical corticosteroid therapy, and the muscularis mucosa in patients with EE and control subjects by using immunohistology. Double immunofluorescence was used to assess mast cell production of TGF-beta 1. The ability of TGF-beta 1 to influence HESM cell contractility was assessed in vitro.Results: In the SM in patients with EE, significantly increased numbers of MCT- and TGF-beta 1-positive cells (but only low levels of eosinophils) were detected compared with those seen in control subjects. MCT expressed TGF-beta 1, which increased the contractility of cultured primary HESM cells in vitro. Topical corticosteroid therapy in patients with EE significantly reduced epithelial MCT numbers but not LP tryptase-chymase-positive mast cell numbers.Conclusions: MCT numbers, rather than eosinophil numbers, are increased in the SM in patients with EE, express TGF-beta 1, and increase the contractility of HESM cells in vitro. As such, mast cells localized to SM in patients with EE might modulate esophageal contractility. (J Allergy Clin Immunol 2010;126:1198-204.)