[慢性阻塞性肺疾病患者和吸烟者CD14+单核细胞上Toll样受体的表达]

[Expression of toll-like receptors on CD14+ monocytes from patients with chronic obstructive pulmonary disease and smokers].

作者信息

Pan Ming-Ming, Sun Tie-Ying, Zhang Hong-Sheng

机构信息

Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2008 Aug 5;88(30):2103-7.

PMID:19080469

Abstract

OBJECTIVE

To investigate the expression of toll-like receptor-2 (TLR2), TLR4 on the CD14+ monocytes of patients with stable chronic obstructive pulmonary disease (COPD) and healthy smokers, and to explore the role of TLR2 and TLR4 in COPD pathogenesis.

METHODS

Thirty COPD patients without evidence of acute exacerbation, 21 healthy smokers, and 25 healthy non-smokers underwent measurement of forced expiratory volume in 1 second (FEV(1))% predicted and FEV(1)/forced vital capacity (FVC) by spirometry. The expression of TLR2 and TLR4 surface molecules on human CD14+ monocytes was assessed using fluorescence activated cell sorter analysis by flow cytometry, expressed as relative mean fluorescence intensity (rmfi) and relative positive cell percent (rpcp), and the correlation of TLR expression with lung function parameters was analyzed.

RESULTS

The rmfi and rpcp of TLR2 on CD14+ monocytes of the COPD patients were (6.3 +/- 1.4)% and (52.9 +/- 20.5)% respectively, both significantly lower than those of the healthy smokers [(8.2 +/- 2.2)% and (73.5 +/- 19.0)% respectively] and those of the nonsmokers [(11.0 +/- 2.4)% and (82.8 +/- 17.9)% respectively, all P < 0.01)]. The rmfi of TLR4 of the COPD patients was 2.2 +/- 0.9, significantly lower than that of the nonsmokers (3.0 +/- 0.5, P < 0.01), while similar to that of the healthy smokers (2.5 +/- 0.6, P > 0.05). The rpcp of TLR4 of the COPD patients (M = 1.3%, Q(1) - Q(3): 0.7% - 2.4%) was significantly lower than that of the healthy smokers (M = 4.7%, Q(1) - Q(3): 2.7% - 9.4%, P < 0.01) and nonsmokers (M = 5.3%, Q(1) - Q(3): 2.6% - 8.4%, P < 0.01). The rmfi of TLR2 and TLR4 on CD14+ monocytes of the healthy smokers was lower than that of the nonsmokers (P < 0.05), while the rpcp of TLR2 and TLR4 on CD14+ monocytes of the healthy smokers was similar to that of the nonsmoker (P < 0.05). The expression of TLR2 and TLR4 on monocytes was positively correlated with the lung function parameters, including FEV(1)% predicted and FEV(1)/FVC (all P < 0.01).

CONCLUSIONS

The expression levels of TLR2 and TLR4 on CD14+ monocytes of the stable COPD patients and healthy smokers decreased significantly. The innate immune response may be depressed in the COPD patients and smokers, and the down-regulation of TLR is associated with reduced lung function parameters.

摘要

目的

探讨稳定期慢性阻塞性肺疾病（COPD）患者及健康吸烟者CD14+单核细胞上Toll样受体2（TLR2）、TLR4的表达情况，以探究TLR2和TLR4在COPD发病机制中的作用。

方法

对30例无急性加重证据的COPD患者、21例健康吸烟者及25例健康非吸烟者进行肺功能测定，通过肺量计测量1秒用力呼气容积（FEV(1)）占预计值百分比及FEV(1)/用力肺活量（FVC）。采用流式细胞术通过荧光激活细胞分选仪分析评估人CD14+单核细胞表面TLR2和TLR4分子的表达，以相对平均荧光强度（rmfi）和相对阳性细胞百分比（rpcp）表示，并分析TLR表达与肺功能参数的相关性。

结果

COPD患者CD14+单核细胞上TLR2的rmfi和rpcp分别为(6.3±1.4)%和(52.9±20.5)%，均显著低于健康吸烟者[(分别为(8.2±2.2)%和(73.5±19.0)%]及非吸烟者[(分别为(11.0±2.4)%和(82.8±17.9)%，P均<0.01)]。COPD患者TLR4的rmfi为2.2±0.9，显著低于非吸烟者（3.0±0.5，P<0.01），而与健康吸烟者相似（2.5±0.6，P>0.05）。COPD患者TLR4的rpcp（M=1.3%，四分位数间距Q(1)-Q(3)：0.7%-2.4%）显著低于健康吸烟者（M=4.7%，Q(1)-Q(3)：2.7%-9.4%，P<0.01）及非吸烟者（M=5.3%，Q(1)-Q(3)：2.6%-8.4%，P<0.01）。健康吸烟者CD14+单核细胞上TLR2和TLR4的rmfi低于非吸烟者（P<0.05），而健康吸烟者CD14+单核细胞上TLR2和TLR4的rpcp与非吸烟者相似（P<0.05）。单核细胞上TLR2和TLR4的表达与肺功能参数呈正相关，包括FEV(1)占预计值百分比及FEV(1)/FVC（P均<0.01）。