Kaur Davinder, Saunders Ruth, Berger Patrick, Siddiqui Salman, Woodman Lucy, Wardlaw Andrew, Bradding Peter, Brightling Christopher E
Institute for Lung Health, and Department of Infection, Inflammation and Immunity, University of Leicester, Leicester, United Kingdom.
Am J Respir Crit Care Med. 2006 Dec 1;174(11):1179-88. doi: 10.1164/rccm.200603-394OC. Epub 2006 Sep 7.
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.
To examine expression of the chemokine receptor, CC chemokine receptor (CCR) 7, in vivo by 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.
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.
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 vivo ASM 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.
The CCL19/CCR7 axis may play an important role in the development of ASM hyperplasia in asthma.
气道平滑肌（ASM）增生是哮喘的一个特征，并随疾病严重程度增加。我们推测这是由于ASM或其祖细胞响应ASM束内ASM或肥大细胞衍生的趋化因子而迁移所致。
通过哮喘患者和健康对照者体内的ASM、ASM原代培养物和成纤维细胞，检测趋化因子受体CC趋化因子受体（CCR）7的表达；确定其配体CC趋化因子配体（CCL）19和CCL21在支气管活检组织、ASM和肥大细胞原代培养物中的表达；并研究CCR7在ASM迁移和修复中的作用。
从支气管镜检查和切除组织中分离ASM。通过免疫组织化学、免疫荧光、流式细胞术、酶联免疫吸附测定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。
ASM、肌成纤维细胞和成纤维细胞表达CCR7。在所有严重程度的哮喘患者中，肥大细胞和血管、重症疾病中的ASM以及离体ASM和肥大细胞在支气管活检组织中高表达CCL19，而非CCL21。CCL19介导的细胞内钙升高和浓度依赖性迁移可激活ASM CCR7，但不影响其增殖。重要的是，肥大细胞和ASM衍生的CCL19介导了ASM的迁移和修复。
CCL19/CCR7轴可能在哮喘中ASM增生的发展中起重要作用。
