Immune response CC chemokines CCL2 and CCL5 are associated with pulmonary sarcoidosis.

Immune response CC chemokines CCL2 and CCL5 are associated with pulmonary sarcoidosis.
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DOI:
10.1186/1755-1536-4-10
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发表时间:
2011-04-04
期刊:
Fibrogenesis & tissue repair
影响因子:
--
通讯作者:
Belperio JA
Belperio JA
中科院分区:
其他
文献类型:
--
作者:
Palchevskiy V;Hashemi N;Weigt SS;Xue YY;Derhovanessian A;Keane MP;Strieter RM;Fishbein MC;Deng JC;Lynch JP 3rd;Elashoff R;Belperio JA

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肺结节病涉及肺部白细胞强烈浸润并形成非坏死性肉芽肿。 CC 趋化因子(趋化因子(C-C 基序)配体 2 (CCL2)-CCL5)是单核细胞的趋化因子,通过七个跨膜 G 偶联受体发挥作用。先前的研究表明,这些趋化因子与结节病之间的关联存在相互矛盾的结果。为了澄清之前的差异,我们对肺结节病患者的支气管肺泡灌洗液 (BALF) 中的 CC 趋化因子进行了迄今为止最大规模的观察性研究。通过酶联免疫吸附测定 (ELISA) 分析了 72 名肺结节病患者的 BALF 趋化因子水平,并与 8 名健康志愿者进行了比较。与对照组相比,肺结节病患者的 BALF CCL3 和 CCL4 水平没有增加。然而,CCL2 和 CCL5 水平升高,亚组分析显示两种趋化因子在肺结节病的所有阶段均较高水平。 CCL2、CCL5、CC趋化因子受体1型(CCR1)、CCR2和CCR3在形成肺肉芽肿的单核细胞中表达,而CCR5仅在肥大细胞上发现。这些数据表明,在肺结节病的所有阶段,CCL2和CCL5是招募表达CCR1、CCR2和CCR3的单核细胞以及表达CCR5的肥大细胞的重要介质。
Pulmonary sarcoidosis involves an intense leukocyte infiltration of the lung with the formation of non-necrotizing granulomas. CC chemokines (chemokine (C-C motif) ligand 2 (CCL2)-CCL5) are chemoattractants of mononuclear cells and act through seven transmembrane G-coupled receptors. Previous studies have demonstrated conflicting results with regard to the associations of these chemokines with sarcoidosis. In an effort to clarify previous discrepancies, we performed the largest observational study to date of CC chemokines in bronchoalveolar lavage fluid (BALF) from patients with pulmonary sarcoidosis. BALF chemokine levels from 72 patients affected by pulmonary sarcoidosis were analyzed by enzyme-linked immunosorbent assay (ELISA) and compared to 8 healthy volunteers. BALF CCL3 and CCL4 levels from pulmonary sarcoidosis patients were not increased compared to controls. However, CCL2 and CCL5 levels were elevated, and subgroup analysis showed higher levels of both chemokines in all stages of pulmonary sarcoidosis. CCL2, CCL5, CC chemokine receptor type 1 (CCR1), CCR2 and CCR3 were expressed from mononuclear cells forming the lung granulomas, while CCR5 was only found on mast cells. These data suggest that CCL2 and CCL5 are important mediators in recruiting CCR1, CCR2, and CCR3 expressing mononuclear cells as well as CCR5-expressing mast cells during all stages of pulmonary sarcoidosis.