Novel site-specific mast cell subpopulations in the human lung

Novel site-specific mast cell subpopulations in the human lung
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DOI:
10.1136/thx.2008.101683
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发表时间:
2009-04-01
期刊:
影响因子:
10
通讯作者:
Erjefalt, J. S.
Erjefalt, J. S.
中科院分区:
医学1区
文献类型:
--
作者:
Andersson, C. K.;Mori, M.;Erjefalt, J. S.

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背景:肺肥大细胞通常分为结缔组织肥大细胞(MCTC)和粘膜肥大细胞(MCT)。这项研究验证了这样的假设,即这些亚型中的每一种都可以进一步划分为由每个解剖肺室内的微环境创造的特定部位的群体。方法:在非炎症条件下,获取手术切除和非吸烟者的支气管镜和经支气管镜活检,以研究肥大细胞。结果:MCT和MCTC同时存在于肺、细支气管和肺泡内,以MCT为主,MCTC在肺血管和胸膜中含量较高。MCTC和MCT的每一种表型都可以进一步分化为特定地点的种群。肺血管的MCTC明显大于小气道壁,而MCT则相反。在每个MCTC和MCT人群中,IgE受体、IL-9受体、肾素、组氨酸脱羧酶、血管内皮生长因子、成纤维细胞生长因子、5-脂氧合酶和白三烯C4合成酶也有不同的部位特异性表达模式(例如,支气管MCT始终比肺泡型MCT表达更多的组氨酸脱羧酶)。血管MCTC的肾素含量较高,而其他房室MCTC的肾素含量明显较低。对于MCTC和MCT,IgE受体在传导气道中高度表达,而在肺泡实质中几乎不表达。结论:这些发现显示了基线条件下肺MCTC和MCT的新的部位特异性亚群。这一观察结果可能对未来探索肥大细胞在一些肺部疾病中的作用具有重要意义。
Background: Lung mast cells are stereotypically divided into connective tissue (MCTC) and mucosal (MCT) mast cells. This study tests the hypothesis that each of these subtypes can be divided further into site-specific populations created by the microenvironment within each anatomical lung compartment.Methods: Surgical resections and bronchial and transbronchial biopsies from non-smoking individuals were obtained to study mast cells under non-inflamed conditions. Morphometric and molecular characteristics of mast cell populations were investigated in multiple lung structures by immunohistochemistry and electron microscopy.Results: MCT and MCTC coexisted in all compartments, with MCT being the prevailing type in bronchi, bronchioles and the alveolar parenchyma and MCTC being more abundant in pulmonary vessels and the pleura. Each of the MCTC and MCT phenotypes could be further differentiated into site-specific populations. MCTC were significantly larger in pulmonary vessels than in small airway walls, while the reverse was observed for MCT. Within each MCTC and MCT population there were also distinct site-specific expression patterns of the IgE receptor, interleukin-9 receptor, renin, histidine decarboxylase, vascular endothelial growth factor, fibroblast growth factor, 5-lipoxygenase and leukotriene C4 synthase (eg, bronchial MCT consistently expressed more histidine decarboxylase than alveolar MCT). Renin content was high in vascular MCTC but markedly lower in MCTC in other compartments. For both MCTC and MCT, the IgE receptor was highly expressed in conducting airways but virtually absent in alveolar parenchyma.Conclusions: These findings demonstrate novel site-specific subpopulations of lung MCTC and MCT at baseline conditions. This observation may have important implications in the future exploration of mast cells in a number of pulmonary diseases.