CCL22 and CCL17 in rat radiation pneumonitis and in human idiopathic pulmonary fibrosis
CCL22 and CCL17 in rat radiation pneumonitis and in human idiopathic pulmonary fibrosis
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DOI：
10.1183/09031936.04.00110203
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发表时间：
2004-07-01
影响因子：
24.3
通讯作者：
Yamaguchi, K
中科院分区：
文献类型：
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作者：
Inoue, T;Fujishima, S;Yamaguchi, K
肺纤维化是由各种已知和未知的病因引起的，但主要的致病机制仍然不明确。趋化因子是一个大家族的趋化细胞因子，在各种炎症疾病中起关键作用。在本研究中，研究了趋化因子在放射性肺炎/肺纤维化大鼠模型中的作用。第28天观察到炎症细胞积聚和肺炎，第56天观察到弥漫性肺泡壁增厚并广泛纤维化。除了先前报道的CCL2（巨噬细胞趋化蛋白-1）诱导外，CCL22（巨噬细胞来源的趋化因子）和CCL17（胸腺和激活调节的趋化因子）的选择性上调也首次在照射后的肺组织中被证实。免疫组织化学表明，CCL22和CCL17主要定位于肺泡巨噬细胞，而它们的受体CC趋化因子受体4 （CCR4）在肺泡淋巴细胞和巨噬细胞中检测到。对特发性肺纤维化和结节病患者支气管肺泡灌洗液的进一步分析发现，在特发性肺纤维化患者中，CCL22水平升高，而CCL17水平未升高。由于这两种趋化因子在各种2型t辅助细胞显性疾病中发挥着关键作用，我们推测CCL22，也可能是CCL17，通过募集CC趋化因子受体4阳性的2型t辅助细胞和肺泡巨噬细胞参与了放射性肺炎/肺纤维化和特发性肺纤维化的病理生理。
Pulmonary fibrosis is caused by various known and unknown aetiologies, but the key pathogenic mechanisms are still ill-defined. Chemokines are a large family of chemotactic cytokines that play pivotal roles in various inflammatory diseases.In the present study, the roles of chemokines in a rat model of radiation pneumonitis/ pulmonary fibrosis were examined.Accumulation of inflammatory cells and pneumonitis were observed on day 28, and diffuse alveolar wall thickening with extensive fibrosis was observed on day 56. In addition to the previously reported CCL2 (macrophage chemoattractant protein-1) induction, selective upregulation of CCL22 (macrophage-derived chemokine) and CCL17 (thymus and activation-regulated chemokine) were demonstrated for the first time in the irradiated lung tissues. Immunohistochemically, it was demonstrated that CCL22 and CCL17 were localised primarily to alveolar macrophages, whereas their receptor CC chemokine receptor 4 (CCR4) was detected on alveolar lymphocytes and macrophages. On further analysis of bronchoalveolar lavage fluid from patients with idiopathic pulmonary fibrosis and sarcoidosis, elevated levels of CCL22, but not of CCL17, were observed in the idiopathic pulmonary fibrosis patients.Since these two chemokines play pivotal roles in various type-2 T-helper cell-dominant diseases, it was speculated that CCL22, and probably CCL17, are involved in the pathophysiology of radiation pneumonitis/pulmonary fibrosis and idiopathic pulmonary fibrosis through the recruitment of CC chemokine receptor 4-positive type-2 T-helper cells and alveolar macrophages.