Airway smooth muscle and mast cell-derived CC chemokine ligand 19 mediate airway smooth muscle migration in asthma
Airway smooth muscle and mast cell-derived CC chemokine ligand 19 mediate airway smooth muscle migration in asthma
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DOI：
10.1164/rccm.200603-394oc
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发表时间：
2006-12-01
影响因子：
24.7
通讯作者：
Brightling, Christopher E.
中科院分区：
文献类型：
--
作者：
Kaur, Davinder;Saunders, Ruth;Brightling, Christopher E.
理由：气道平滑肌（ASM）增生是哮喘的一个特征，并随着病情的严重程度而增加。我们假设这是由于ASM或祖细胞响应来自ASM或ASM束内肥大细胞的趋化因子而迁移的结果。目的：检测哮喘患者和健康对照者体内ASM中趋化因子受体CC趋化因子受体（CCR） 7的表达，以及ASM和成纤维细胞的原代培养；确定其配体，CC趋化因子配体（CCL） 19和CCL21在支气管活检和ASM和肥大细胞原代培养中的表达；并研究CCR7在ASM迁移和修复中的作用。方法：从支气管镜下分离ASM并切除组织。通过免疫组织化学、免疫荧光、流式细胞术、ELISA和逆转录聚合酶链反应检测受体和趋化因子的表达。通过细胞内钙测量、趋化性、伤口愈合试验和细胞增殖测量来检测CCR7的功能。测量和主要结果：ASM、肌成纤维细胞和成纤维细胞表达CCR7。CCL19，而不是CCL21，在所有严重哮喘的肥大细胞和血管的支气管活检中，在严重疾病的ASM中，以及在离体ASM和肥大细胞中都有高表达。通过ccl19介导的细胞内钙升高和浓度依赖性迁移激活ASM CCR7，但不增殖。重要的是，肥大细胞和ASM衍生的CCL19介导了ASM的迁移和修复。结论：CCL19/CCR7轴可能在哮喘ASM增生过程中起重要作用。
Rationale:Airway smooth muscle (ASM) hyperplasia is a feature of asthma, and increases with disease severity. We hypothesized that this results from migration of ASM or progenitors in response to chemokines derived from ASM or mast cells within the ASM bundle.Objectives:To examine expression of the chemokine receptor, CC chemokine receptor (CCR) 7,in vivoby ASM in patients with asthma and healthy control subjects, and by primary cultures of ASM and fibroblasts; to define expression of its ligands, CC chemokine ligand (CCL) 19 and CCL21, in bronchial biopsies, and primary cultures of ASM and mast cells; and to investigate CCR7's role in ASM migration and repair.Methods:ASM was isolated from bronchoscopy and resection tissue. Receptor and chemokine expression was examined by immunohistochemistry, immunofluorescence, flow cytometry, ELISA, and reverse transcriptase–polymerase chain reaction. CCR7 function was examined by intracellular calcium measurements, chemotaxis, wound healing assays, and measurement of cell proliferation.Measurements and Main Results:ASM, myofibroblasts, and fibroblasts expressed CCR7. CCL19, but not CCL21, was highly expressed in bronchial biopsies by mast cells and vessels in asthma of all severities, ASM in severe disease, and ex vivoASM and mast cells. ASM CCR7 activation by CCL19-mediated intracellular calcium elevation and concentration-dependent migration, but not proliferation. Importantly, mast cell and ASM-derived CCL19 mediated ASM migration and repair.Conclusions:The CCL19/CCR7 axis may play an important role in the development of ASM hyperplasia in asthma.