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COPD 患者单核细胞向 CXCR3 和 CCR5 趋化因子的迁移增强。

Enhanced monocyte migration to CXCR3 and CCR5 chemokines in COPD.

出版信息

Eur Respir J. 2016 Apr;47(4):1093-102. doi: 10.1183/13993003.01642-2015.

DOI:10.1183/13993003.01642-2015
PMID:26965295
Abstract

Chronic obstructive pulmonary disease (COPD) patients exhibit chronic inflammation, both in the lung parenchyma and the airways, which is characterised by an increased infiltration of macrophages and T-lymphocytes, particularly CD8+ cells. Both cell types can express chemokine (C-X-C motif) receptor (CXCR)3 and C-C chemokine receptor 5 and the relevant chemokines for these receptors are elevated in COPD. The aim of this study was to compare chemotactic responses of lymphocytes and monocytes of nonsmokers, smokers and COPD patients towards CXCR3 ligands and chemokine (C-C motif) ligand (CCL)5. Migration of peripheral blood mononuclear cells, monocytes and lymphocytes from nonsmokers, smokers and COPD patients toward CXCR3 chemokines and CCL5 was analysed using chemotaxis assays. There was increased migration of peripheral blood mononuclear cells from COPD patients towards all chemokines studied when compared with nonsmokers and smokers. Both lymphocytes and monocytes contributed to this enhanced response, which was not explained by increased receptor expression. However, isolated lymphocytes failed to migrate and isolated monocytes from COPD patients lost their enhanced migratory capacity. Both monocytes and lymphocytes cooperate to enhance migration towards CXCR3 chemokines and CCL5. This may contribute to increased numbers of macrophages and T-cells in the lungs of COPD patients, and inhibition of recruitment using selective antagonists might be a treatment to reduce the inflammatory response in COPD.

摘要

慢性阻塞性肺疾病(COPD)患者表现出肺部和气道的慢性炎症,其特征为巨噬细胞和 T 淋巴细胞浸润增加,特别是 CD8+细胞。这两种细胞类型都可以表达趋化因子(C-X-C 基序)受体(CXCR)3 和 C-C 趋化因子受体 5,COPD 患者中这些受体的相关趋化因子升高。本研究的目的是比较非吸烟者、吸烟者和 COPD 患者的淋巴细胞和单核细胞对 CXCR3 配体和趋化因子(C-C 基序)配体(CCL)5 的趋化反应。使用趋化实验分析了外周血单核细胞、单核细胞和淋巴细胞从非吸烟者、吸烟者和 COPD 患者向 CXCR3 趋化因子和 CCL5 的迁移。与非吸烟者和吸烟者相比,COPD 患者的外周血单核细胞向所有研究的趋化因子的迁移增加。这种增强的反应不仅是由于受体表达增加所致,淋巴细胞和单核细胞都对此反应有贡献。然而,来自 COPD 患者的分离淋巴细胞未能迁移,而分离的单核细胞则丧失了增强的迁移能力。单核细胞和淋巴细胞共同增强对 CXCR3 趋化因子和 CCL5 的迁移。这可能导致 COPD 患者肺部巨噬细胞和 T 细胞数量增加,使用选择性拮抗剂抑制募集可能是减轻 COPD 炎症反应的一种治疗方法。

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