INTERLEUKIN-4, INTERLEUKIN-5, AND INTERLEUKIN-6 AND TUMOR-NECROSIS-FACTOR-ALPHA IN NORMAL AND ASTHMATIC AIRWAYS - EVIDENCE FOR THE HUMAN MAST-CELL AS A SOURCE OF THESE CYTOKINES
INTERLEUKIN-4, INTERLEUKIN-5, AND INTERLEUKIN-6 AND TUMOR-NECROSIS-FACTOR-ALPHA IN NORMAL AND ASTHMATIC AIRWAYS - EVIDENCE FOR THE HUMAN MAST-CELL AS A SOURCE OF THESE CYTOKINES
复制标题
DOI：
10.1165/ajrcmb.10.5.8179909
复制
发表时间：
1994-05-01
影响因子：
6.4
通讯作者：
HOLGATE, ST
中科院分区：
文献类型：
--
作者：
BRADDING, P;ROBERTS, JA;HOLGATE, ST
哮喘的特征是支气管粘膜中存在由活化的肥大细胞、嗜酸性粒细胞和 T 细胞组成的炎症细胞浸润。多种细胞因子被认为在这种反应中发挥着关键作用，特别是白细胞介素 (IL)-4、IL-5、IL-6 和肿瘤坏死因子-α (TNF-α)。在这项研究中，我们使用免疫组织化学应用于支气管粘膜活检的甲基丙烯酸乙二醇酯薄切片，以确定正常和哮喘气道中这些细胞因子的细胞来源。哮喘粘膜和正常粘膜都含有大量对所有四种细胞因子染色呈阳性的细胞，其中大多数根据其类胰蛋白酶含量被鉴定为肥大细胞。哮喘活检中嗜酸性粒细胞也导致了一些 IL-5 免疫染色。通过使用两种针对 IL-4 不同表位的单克隆抗体，我们为哮喘中 IL-4 分泌增强提供了初步证据。同样，哮喘活检中 TNF-α 染色的肥大细胞数量增加了七倍，表明这种细胞因子在这种疾病中也上调。这些发现清楚地表明人类肥大细胞是 IL-4、IL-5、IL-6 和 TNF-α 的来源，并补充了这样的观点：肥大细胞与 T 细胞一起，可能在哮喘炎症反应的启动和维持中发挥重要作用。
Asthma is characterized by the presence of an inflammatory cell infiltrate in the bronchial mucosa consisting of activated mast cells, eosinophils, and T cells. Several cytokines are considered to play a pivotal role in this response, particularly interleukin (IL)-4, IL-5, IL-6, and tumor necrosis factor-alpha (TNF-alpha). In this study, we have used immunohistochemistry applied to thin glycol methacrylate sections of bronchial mucosal biopsies to define the cellular provenance of these cytokines in normal and asthmatic airways. Both the asthmatic and normal mucosa contained numerous cells staining positively for all four cytokines, with the majority identified as mast cells by their tryptase content. Eosinophils also accounted for some IL-5 immunostaining in the asthmatic biopsies. By using two monoclonal antibodies directed to different epitopes of IL-4, we provide tentative evidence for enhanced IL-4 secretion in asthma. Similarly, a sevenfold increase in the number of mast cells staining for TNF-alpha in the asthmatic biopsies suggests that this cytokine is also up-regulated in this disease. These findings clearly identify human mast cells as a source of IL-4, IL-5, IL-6, and TNF-alpha and add to the view that, along with T cells, mast cells may play an important role in initiating and maintaining the inflammatory response in asthma.