CCL2 release by airway smooth muscle is increased in asthma and promotes fibrocyte migration.
CCL2 release by airway smooth muscle is increased in asthma and promotes fibrocyte migration.
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DOI：
10.1111/all.12444
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发表时间：
2014-09
期刊：
影响因子：
12.4
通讯作者：
Brightling CE
中科院分区：
文献类型：
--
作者：
Singh SR;Sutcliffe A;Kaur D;Gupta S;Desai D;Saunders R;Brightling CE
哮喘的特征在于可变的气流阻塞、气道炎症、气道高反应性和气道重塑。气道平滑肌（ASM）增生是气道重塑的特征，并导致支气管壁增厚。我们试图研究趋化因子在哮喘患者与健康对照的ASM细胞原代培养物中的表达水平，并评估差异表达的趋化因子是否（i）促进纤维细胞（FC）向ASM迁移，以及（ii）在哮喘受试者的血液和支气管壁增厚的哮喘患者的痰液样本中增加。通过MesoScale Discovery平台测量由原代ASM释放的趋化因子浓度。与健康对照组相比，哮喘患者ASM中最高表达的趋化因子通过ELISA确认，其同源趋化因子受体通过FC的表达通过免疫荧光和流式细胞术检查。这种趋化因子在FC迁移到ASM的作用进行了研究，通过趋化性测定。与健康对照组相比，哮喘患者原代ASM上清液中趋化因子（C-C基序）配体2（CCL 2）水平升高。CCR 2在FC上表达。纤维细胞向重组CCL 2和ASM上清液迁移。这些作用被CCL 2中和所抑制。与健康对照组相比，哮喘患者血液中的CCL 2水平升高，并且在支气管壁增厚的哮喘患者中痰中CCL 2升高。气道平滑肌来源的CCL 2介导FC迁移并可能促进哮喘中ASM增生的发展。
Asthma is characterized by variable airflow obstruction, airway inflammation, airway hyper-responsiveness and airway remodelling. Airway smooth muscle (ASM) hyperplasia is a feature of airway remodelling and contributes to bronchial wall thickening. We sought to investigate the expression levels of chemokines in primary cultures of ASM cells from asthmatics vs healthy controls and to assess whether differentially expressed chemokines (i) promote fibrocyte (FC) migration towards ASM and (ii) are increased in blood from subjects with asthma and in sputum samples from those asthmatics with bronchial wall thickening. Chemokine concentrations released by primary ASM were measured by MesoScale Discovery platform. The chemokine most highly expressed by ASM from asthmatics compared with healthy controls was confirmed by ELISA, and expression of its cognate chemokine receptor by FCs was examined by immunofluorescence and flow cytometry. The role of this chemokine in FC migration towards ASM was investigated by chemotaxis assays. Chemokine (C-C motif) ligand 2 (CCL2) levels were increased in primary ASM supernatants from asthmatics compared with healthy controls. CCR2 was expressed on FCs. Fibrocytes migrated towards recombinant CCL2 and ASM supernatants. These effects were inhibited by CCL2 neutralization. CCL2 levels were increased in blood from asthmatics compared with healthy controls, and sputum CCL2 was increased in asthmatics with bronchial wall thickening. Airway smooth muscle-derived CCL2 mediates FC migration and potentially contributes to the development of ASM hyperplasia in asthma.
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DOI：
10.4049/jimmunol.181.4.2772
发表时间：
2008-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hollins F;Kaur D;Yang W;Cruse G;Saunders R;Sutcliffe A;Berger P;Ito A;Brightling CE;Bradding P
通讯作者：
Bradding P
DOI：
10.1164/rccm.200603-394oc
发表时间：
2006-12-01
影响因子：
24.7
作者：
Kaur, Davinder;Saunders, Ruth;Brightling, Christopher E.
通讯作者：
Brightling, Christopher E.
影响因子：
4.8
作者：
Nie, M;Corbett, L;Pang, LH
通讯作者：
Pang, LH
DOI：
10.4049/jimmunol.1200689
发表时间：
2012-09-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Roy RM;Wüthrich M;Klein BS
通讯作者：
Klein BS
影响因子：
9.6
作者：
Gupta, Sumit;Siddiqui, Salman;Brightling, Christopher E.
通讯作者：
Brightling, Christopher E.