慢性阻塞性肺疾病患者诱导痰中的CXCR3和CCR5趋化因子

CXCR3 and CCR5 chemokines in induced sputum from patients with COPD.

作者信息

Costa Claudia, Rufino Rogerio, Traves Suzanne L, Lapa E Silva Jose Roberto, Barnes Peter J, Donnelly Louise E

机构信息

Airway Disease, National Heart and Lung Institute, Imperial College, London, SW3 6LY, UK.

出版信息

Chest. 2008 Jan;133(1):26-33. doi: 10.1378/chest.07-0393. Epub 2007 Oct 9.

DOI:10.1378/chest.07-0393

PMID:17925429

Abstract

BACKGROUND

COPD is associated with increased numbers of CD4(+) and CD8(+) lymphocytes and macrophages in the small airways and lung parenchyma. The chemokines regulating T-cell recruitment into the lung are unknown but may involve CXCR3 and CCR5 chemoattractants. The aims of this study were to determine the concentrations of CXCR3 chemokines CXCL9, CXCL10, CXCL11, and the CCR5 chemokine CCL5 in induced sputum from patients with COPD, smokers, and nonsmokers, and to examine the relationship between chemokine expression, inflammatory cells, and airway obstruction.

METHODS

Differential cell counts were performed and concentrations of CXCL9, CXCL10, CXCL11, and CCL5 were measured in induced sputum from nonsmokers (n = 18), smokers (n = 20), and COPD patients (n = 35) using an enzyme-linked immunosorbent assay.

RESULTS

Concentrations of CXCL9, CXCL10, CXCL11, and CCL5 were significantly increased in the sputum of patients with COPD when compared with nonsmokers but not smokers without obstruction: CXCL9 (median, 14.3 pg/mL; interquartile range [IQR], 6.5 to 99.3; vs median, 1.4 pg/mL; IQR, 0 to 10.4 [p < 0.001]; vs 8.5 pg/mL; IQR, 0 to 16.0, respectively); CXCL10 (16.9 pg/mL; IQR, 6.2 to 148.8; vs 3.7 pg/mL; IQR, 0 to 18.8 [p < 0.05]; vs 11.3 pg/mL; IQR, 3.7 to 46.7); CXCL11 (58.1 pg/mL; IQR, 34.5 to 85.3; vs 33.5 pg/mL; IQR, 23.2 to 49.7 [p < 0.05]; vs 49.8 pg/mL; IQR, 32.6 to 105.6); and CCL5 (59.9 pg/mL; IQR, 57.1 to 67.8; vs 33.5 pg/mL; IQR, 31.6 to 36.9 [p < 0.001]). CCL5 in sputum from smokers was also significantly increased compared with that from nonsmokers (median, 63.0 pg/mL; IQR, 60.8 to70.2; p < 0.001). There was a negative correlation between FEV(1) percentage of predicted, FEV(1)/FVC ratio, and percentage of macrophages, and all the chemokines analyzed. Neutrophil numbers correlated positively with the concentrations of chemokines.

CONCLUSIONS

CXCR3 chemokines and CCL5 are increased in sputum from COPD patients compared with nonsmokers, and may be important in COPD pathogenesis.

摘要

背景

慢性阻塞性肺疾病（COPD）与小气道及肺实质中CD4(+)和CD8(+)淋巴细胞以及巨噬细胞数量增加有关。调节T细胞向肺内募集的趋化因子尚不清楚，但可能涉及CXCR3和CCR5趋化因子。本研究旨在测定COPD患者、吸烟者和非吸烟者诱导痰中CXCR3趋化因子CXCL9、CXCL10、CXCL11以及CCR5趋化因子CCL5的浓度，并研究趋化因子表达、炎症细胞与气道阻塞之间的关系。

方法

对非吸烟者（n = 18）、吸烟者（n = 20）和COPD患者（n = 35）的诱导痰进行细胞分类计数，并采用酶联免疫吸附测定法测量CXCL9、CXCL10、CXCL11和CCL5的浓度。

结果

与非吸烟者相比，COPD患者痰中CXCL9、CXCL10、CXCL11和CCL5的浓度显著升高，但与无气流受限的吸烟者相比无显著差异：CXCL9（中位数，14.3 pg/mL；四分位间距[IQR]，6.5至99.3；vs中位数，1.4 pg/mL；IQR，0至10.4 [p < 0.001]；vs 8.5 pg/mL；IQR，0至16.0）；CXCL10（16.9 pg/mL；IQR，6.2至148.8；vs 3.7 pg/mL；IQR，0至18.8 [p < 0.05]；vs 11.3 pg/mL；IQR，3.7至46.7）；CXCL11（58.1 pg/mL；IQR，34.5至85.3；vs 33.5 pg/mL；IQR，23.2至49.7 [p < 0.05]；vs 49.8 pg/mL；IQR，32.6至105.6）；以及CCL5（59.9 pg/mL；IQR，57.1至67.8；vs 33.5 pg/mL；IQR，31.6至36.9 [p < 0.001]）。吸烟者痰中的CCL5与非吸烟者相比也显著升高（中位数，63.0 pg/mL；IQR，60.8至70.2；p < 0.001）。预测的第一秒用力呼气容积（FEV(1)）百分比、FEV(1)/用力肺活量（FVC）比值以及巨噬细胞百分比与所有分析的趋化因子之间呈负相关。中性粒细胞数量与趋化因子浓度呈正相关。