Heterogeneity of human mast cells based on cytokine content.
Heterogeneity of human mast cells based on cytokine content.
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基于细胞因子含量的人类肥大细胞的异质性。
DOI：
10.4049/jimmunol.155.1.297
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发表时间：
1995
影响因子：
4.4
通讯作者：
S. Holgate
中科院分区：
文献类型：
--
作者：
P. Bradding;Y. Okayama;P. Howarth;M. Church;S. Holgate
根据中性丝氨酸蛋白酶的含量，人类肥大细胞可以分为两种不同的表型，这表明它们具有不同的生物学和病理学作用。最近，研究表明人类肥大细胞是多种多效性细胞因子的来源，包括IL-4、IL-5、IL-6、IL-8和tnf - α，但并非所有肥大细胞都含有所有这些细胞因子，这表明细胞因子的表达也存在功能异质性。在本研究中，我们利用免疫组织化学方法检测了肥大细胞中性蛋白酶表达与细胞因子含量之间的关系。5例正常人和5例过敏性哮喘患者的支气管黏膜活检，5例正常人和3例变应性鼻炎患者的鼻黏膜活检均包埋于甲基丙烯酸乙二醇酯中。在2微米的切片上染色IL-4、IL-5和IL-6，相邻的切片上染色胰蛋白酶和切酶。细胞因子在胰蛋白酶+乳糜酶-肥大细胞（MCT）和胰蛋白酶+乳糜酶+肥大细胞（MCTC）中的分布通过荧光相机在MCTC或MCT上连续切片共定位来检测。尽管IL-4在两种肥大细胞表型中都有分布，但它在MCTC亚群中优先表达（总体85% MCTC:15% MCT）。相比之下，IL-5和IL-6几乎仅限于MCT亚群。分离的皮肤肥大细胞（> 99% MCTC）的免疫染色支持这些发现，对IL-4有很强的免疫反应性，但对IL-5或IL-6的免疫反应性很低。这些结果表明，除了分泌颗粒的中性蛋白酶含量表现出异质性外，人肥大细胞在细胞因子含量方面也表现出异质性。这表明MCTC和MCT细胞的生物学功能不同，因为它们产生和释放不同细胞因子的能力不同。
Human mast cells can be divided into two distinct phenotypes based on their content of neutral serine proteases, suggesting that they serve differing biologic and pathologic roles. Recently, it has been demonstrated that human mast cells are a source of several pleiotropic cytokines including IL-4, IL-5, IL-6, IL-8, and TNF-alpha, but not all mast cells contain all of these cytokines, suggesting that there is also functional heterogeneity with respect to cytokine expression. In this study, we have examined the relationship between mast cell neutral protease expression and cytokine content using immunohistochemistry. Bronchial mucosal biopsies from five normal subjects and five patients with allergic asthma, and nasal mucosal biopsies from five normal subjects and three patients with allergic rhinitis were embedded in glycol methacrylate. Sections (2 microns) were stained for IL-4, IL-5, and IL-6, adjacent to serial sections stained for tryptase and chymase. The distribution of cytokines among the tryptase+ chymase- mast cells (MCT) and tryptase+ chymase+ mast cells (MCTC) was examined by co-localization of cytokines to MCTC or MCT in serial sections using the camera-lucida. Although IL-4 was distributed among both mast cell phenotypes, it was expressed preferentially by the MCTC subset (overall 85% MCTC:15% MCT). In contrast, IL-5 and IL-6 were restricted almost exclusively to the MCT subset. Immunostaining of isolated skin mast cells (> 99% MCTC) supported these findings, with strong immunoreactivity present for IL-4 but very little for IL-5 or IL-6. These results indicate that in addition to exhibiting heterogeneity with respect to neutral protease content of the secretory granules, human mast cells are also heterogeneous with respect to cytokine content. This suggests that the biologic functions of MCTC and MCT cells differ as a result of their capacity to generate and release different cytokine profiles.