Increased expression of the chemokine receptor CXCR3 and its ligand CXCL10 in peripheral airways of smokers with chronic obstructive pulmonary disease
Increased expression of the chemokine receptor CXCR3 and its ligand CXCL10 in peripheral airways of smokers with chronic obstructive pulmonary disease
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DOI：
10.1164/rccm.2107139
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发表时间：
2002-05-15
影响因子：
24.7
通讯作者：
Fabbri, LM
中科院分区：
文献类型：
--
作者：
Saetta, M;Mariani, M;Fabbri, LM
CXCR3是一种趋化因子受体，主要表达于淋巴细胞，尤其是1型T淋巴细胞。患有慢性阻塞性肺疾病(COPD)的吸烟者患有慢性支气管炎，其特征是T淋巴细胞在呼吸道和肺实质中的渗透增加，特别是CD8(+)。为探讨CXCR3及其配体干扰素诱导蛋白10/CXCL10在慢性阻塞性肺疾病(COPD)中的表达，对19例因肺内局限性病变而行肺切除的患者外周呼吸道进行CXCR3(+)细胞计数和CXCL10表达分析。我们检测了7名固定气流受限(COPD)吸烟者、5名肺功能正常的吸烟者和7名肺功能正常的非吸烟者的肺标本。免疫组织化学方法检测CXCR3(+)细胞在外周呼吸道上皮、粘膜下层和外膜中的数量。COPD吸烟组上皮和粘膜下层CXCR3(+)细胞数较非吸烟组增加，但与肺功能正常的吸烟组比较差异无统计学意义。CXCR3配体CXCL10在吸烟COPD患者的细支气管上皮细胞中呈阳性表达，而在吸烟和不吸烟对照组的细支气管上皮细胞中未见表达。大多数CXCR3(+)细胞共表达CD8并产生干扰素-γ。这些发现提示CXCR3/CXCL10轴可能参与了COPD吸烟者外周呼吸道的T细胞募集，这些T细胞可能具有1型特征。
CXCR3 is a chemokine receptor preferentially expressed on lymphocytes, particularly on type-1 T-lymphocytes. Smokers who develop chronic obstructive pulmonary disease (COPD) have a chronic bronchopulmonary inflammation that is characterized by an increased infiltration of T-lymphocytes, particularly CD8(+), in the airways and lung parenchyma. To investigate the expression of CXCR3 and its ligand interferon-induced protein 10/CXCL10 in COPD, we counted the number of CXCR3(+) cells and analyzed the expression of CXCL10 in the peripheral airways of 19 patients undergoing lung resection for localized pulmonary lesions. We examined lung specimens from seven smokers with fixed airflow limitation (COPD), five smokers with normal lung function, and seven nonsmoking subjects with normal lung function. The number of CXCR3(+) cells was immunohistochemically quantified in the epithelium, in the submucosa, and in the adventitia of peripheral airways. The number of CXCR3(+) cells in the epithelium and submucosa was increased in smokers with COPD as compared with nonsmoking subjects, but not as compared with smokers with normal lung function. Immunoreactivity for the CXCR3-ligand CXCL10 was present in the bronchiolar epithelium of smokers with COPD but not in the bronchiolar epithelium of smoking and nonsmoking control subjects. Most CXCR3(+) cells coexpressed CD8 and produced interferon gamma. These findings suggest that the CXCR3/CXCL10 axis may be involved in the T cell recruitment that occurs in peripheral airways of smokers with COPD and that these T cells may have a type-1 profile.