IgE-dependent TSLP production by human mast cells and the role of mast cell-derived TSLP in bronchial asthma

为探讨胸腺基质淋巴生成素(TSLP)在哮喘支气管黏膜中的表达，应用免疫组织化学方法检测了16例哮喘患者和11例正常对照肺组织中TSLP的表达。哮喘患者呼吸道中90%以上的肥大细胞为肥大细胞，且肥大细胞数量显著增加(P&lt；0.0001)。TSLP~+肥大细胞数与血清IgE水平、高反应性、血和痰中嗜酸粒细胞计数呈显著正相关，提示肥大细胞来源的TSLP可能在哮喘发病机制中起重要作用。FcεRI介导的人肥大细胞表达上调5.2±2.9倍，IL 4显著增强FcεRI介导的TSLP m RNA表达(5 3.7±15.9倍，P<0.0 5)，而脂多糖和PolyI：C不能诱导TSLP m RNA的表达。我们证实，在有蛋白酶抑制剂存在的情况下，MC小球和肥大细胞培养上清液中有TSLP的产生，提示肥大细胞是哮喘中TSLP的主要来源之一。

To investigate the thymic stromal lymphopoietin (TSLP) expression in asthmatic bronchial mucosa, we determined the cell populations expressing TSLP in the lungs of 16 asthmatics and of 11 controls by using immunohistochemistry. Ninety % of TSLP^+ cells were mast cells in the airways and the number of TSLP^+ mast cells was significantly increased in the airways of asthmatics (P < 0.0001). There was a significant correlation between the number of TSLP^+ mast cells and serum IgE level, hyperresponsibility, eosinophil count in the blood and the sputum, suggesting that mast cell-derived TSLP may play an important role in the pathogenesis of asthma. FcεRI-mediated activation of human mast cells upregulated TSLP mRNA expression 5.2±2.9 fold, and IL-4 significantly enhanced the FcεRI-mediated expression (53.7±15.9 fold, P< 0.05), but LPS and polyI : C failed to induce TSLP mRNA. We confirmed the production of TSLP in MC pellets and mast cell supernatants after activation in the presence of protease inhibitors, indicating mast cells are one of the main sources of TSLP in bronchial asthma.