CXCR3 and CCR5 chemokines in induced sputum from patients with COPD
CXCR3 and CCR5 chemokines in induced sputum from patients with COPD
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DOI：
10.1378/chest.07-0393
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发表时间：
2008-01-01
期刊：
影响因子：
9.6
通讯作者：
Donnelly, Louise E.
中科院分区：
文献类型：
--
作者：
Costa, Claudia;Rufino, Rogerio;Donnelly, Louise E.
背景：COPD与小气道和肺实质中CD4（+）和CD8（+）淋巴细胞和巨噬细胞数量增加有关。调节t细胞募集进入肺的趋化因子尚不清楚，但可能涉及CXCR3和CCR5趋化剂。本研究的目的是测定慢性阻塞性肺病患者、吸烟者和非吸烟者诱导痰中CXCR3趋化因子CXCL9、CXCL10、CXCL11和CCR5趋化因子CCL5的浓度，并研究趋化因子表达、炎症细胞和气道阻塞之间的关系。方法：采用酶联免疫吸附法对非吸烟者（n = 18）、吸烟者（n = 20）和COPD患者（n = 35）的诱导痰进行细胞计数和CXCL9、CXCL10、CXCL11和CCL5的浓度测定。结果：COPD患者痰中CXCL9、CXCL10、CXCL11和CCL5的浓度与不吸烟但不吸烟且无梗阻的患者相比显著升高：CXCL9（中位数为14.3 pg/mL，四分位数范围[IQR]为6.5 ~ 99.3，中位数为1.4 pg/mL， IQR为0 ~ 10.4 [p < 0.001]，中位数为8.5 pg/mL， IQR为0 ~ 16.0）；CXCL10 (16.9 pg/mL； IQR, 6.2 ~ 148.8; vs . 3.7 pg/mL； IQR, 0 ~ 18.8 [p < 0.05]; vs . 11.3 pg/mL； IQR, 3.7 ~ 46.7)；CXCL11 (58.1 pg/mL， IQR为34.5 ~ 85.3，对33.5 pg/mL； IQR为2.3.2 ~ 49.7 [p < 0.05]；对49.8 pg/mL， IQR为32.6 ~ 105.6)；CCL5 （59.9 pg/mL； IQR, 57.1 ~ 67.8；对33.5 pg/mL； IQR, 31.6 ~ 36.9 [p < 0.001]）。与非吸烟者相比，吸烟者痰中的CCL5也显著增加（中位数为63.0 pg/mL； IQR为60.8 ~ 70.2;p < 0.001）。FEV1预测百分比、FEV1/FVC比值、巨噬细胞百分比与所有趋化因子均呈负相关。中性粒细胞数量与趋化因子浓度呈正相关。结论：与非吸烟者相比，COPD患者痰中CXCR3趋化因子和CCL5升高，可能在COPD发病机制中起重要作用。
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, 2.3.2 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 to 70.2; p < 0.001). There was a negative correlation between FEV1 percentage of predicted, FEV1/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.