Bellini A, Yoshimura H, Vittori E, Marini M, Mattoli S
Diagnostic Center for Respiratory and Allergic Diseases, Institute of Experimental Medicine, Milan, Italy.
J Allergy Clin Immunol. 1993 Sep;92(3):412-24. doi: 10.1016/0091-6749(93)90120-5.
T lymphocytes may orchestrate the inflammatory response in atopic asthma, but the mechanisms that promote T-cell accumulation in asthmatic airways are still unclear. In this study, we tested the hypothesis that bronchial epithelial cells of patients with atopic asthma release chemoattractant factors for T lymphocytes.
Sixteen patients with atopic asthma and eight healthy control subjects were selected for this study. Bronchial epithelial cells were isolated from biopsy specimens obtained by means of bronchoscopy and cultured for 48 hours in serum- and hormone-free medium, with or without 10(-6) mol/L histamine.
Only the supernatants of cells from donors with asthma showed chemotactic activity for T lymphocytes, and this was significantly increased (p < 0.025) by exposure to histamine. Chemotactic activity was in part mediated by interleukin-8 (IL-8), because an antibody against human IL-8 significantly reduced it (p < 0.05) and the cell supernatants contained appreciable amounts of immunoreactive IL-8 (0.89 +/- 0.39 ng/ml). Both the residual chemotactic activity of unstimulated epithelial cells and the increased activity caused by histamine were mediated by a single protease-sensitive substance with an apparent molecular weight of 56,000 d and an estimated isoelectric point of 8.8 to 9.1. The partially purified chemoattractant specifically enhanced the migration of CD4+ T lymphocytes, and its activity was inhibited by the univalent Fab fragment of a monoclonal antibody against CD4.
These results extend our previous observations, indicating an important effector role of bronchial epithelium in asthma.
T淋巴细胞可能在特应性哮喘的炎症反应中起协调作用，但促进T细胞在哮喘气道中积聚的机制仍不清楚。在本研究中，我们检验了以下假设：特应性哮喘患者的支气管上皮细胞释放T淋巴细胞趋化因子。
本研究选取了16例特应性哮喘患者和8名健康对照者。通过支气管镜检查获取活检标本，从中分离出支气管上皮细胞，并在无血清和无激素的培养基中培养48小时，培养基中添加或不添加10(-6)mol/L组胺。
仅哮喘患者供体的细胞上清液对T淋巴细胞显示趋化活性，且暴露于组胺后趋化活性显著增强（p<0.025）。趋化活性部分由白细胞介素-8（IL-8）介导，因为抗人IL-8抗体可显著降低趋化活性（p<0.05），且细胞上清液中含有可观量的免疫反应性IL-8（0.89±0.39ng/ml）。未刺激的上皮细胞的残余趋化活性以及组胺引起的活性增强均由一种表观分子量为56,000d、估计等电点为8.8至9.1的单一蛋白酶敏感物质介导。部分纯化的趋化因子特异性增强了CD4+T淋巴细胞的迁移，其活性被抗CD4单克隆抗体的单价Fab片段抑制。
这些结果扩展了我们之前的观察结果，表明支气管上皮在哮喘中起重要的效应作用。
