[Expression of toll-like receptors on CD14+ monocytes from patients with chronic obstructive pulmonary disease and smokers].
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.
Pan
Ming-Ming
MM
Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.
Sun
Tie-Ying
TY
Zhang
Hong-Sheng
HS
D000368:Aged; D005260:Female; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis*; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000503:physiopathology; D012907:Smoking / Q000097:blood / Q000503:physiopathology; D051193:Toll-Like Receptors / Q000096:biosynthesis*
D018950:Lipopolysaccharide Receptors; D051193:Toll-Like Receptors