[Relationships between the expressions of intercellular adhesion molecule-1 and tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-9 in lung tissues of patients with chronic obstructive pulmonary disease].
OBJECTIVE
To evaluate the correlation between the expressions of intercellular adhesion molecule-1 (ICAM-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) and matrix metalloproteinase-9 (MMP-9) in lung tissues of patients with COPD.


METHODS
Lung tissues from patients with COPD (COPD group, n = 19) and those without COPD (smokers and nonsmokers with normal lung function, n = 11 and 9, respectively) were obtained from surgical excisions of lung cancer patients. The mRNA expression of ICAM-1, TIMP-1 and MMP-9 was detected using semi-quantitative RT-PCR. The protein expression of ICAM-1, TIMP-1 and MMP-9 was detected by using immunohistochemistry method.


RESULTS
There were significant differences in FEV1% and FEV1/FVC% among smokers without COPD, nonsmokers without COPD and COPD patients. MMP-9 was highly expressed in alveolar epithelial cells, bronchial epithelial cells, vascular smooth muscle cells, alveolar macrophages, and interstitial cells in the COPD group, compared with smokers without COPD group and nonsmokers without COPD group (54.0 +/- 15.0), (1.2 +/- 0.7) and (1.4 +/- 0.8). Low level expression of TIMP-1 was detected in alveolar macrophages, alveolar epithelial cells and vascular smooth muscle cells in the COPD group, but no expression in smokers and nonsmokers without COPD. High level expression of ICAM-1 was detected in alveolar epithelial cells, and the expression was higher in the COPD group (52.1 +/- 13.4), (2.1 +/- 1.1) and (4.5 +/- 2.4). The mRNA level of MMP-9 showed significant difference among patients with COPD, smokers without COPD and nonsmokers without COPD (0.71 +/- 0.16), (0.20 +/- 0.08) and (0.17 +/- 0.05). The mRNA level of TIMP-1 was also significantly different among patients with COPD, smokers without COPD and nonsmokers without COPD (0.47 +/- 0.10), (0.26 +/- 0.08) and (0.20 +/- 0.06). ICAM expression was also significantly higher in patients with COPD as compared with smokers without COPD and nonsmokers without COPD (0.62 +/- 0.15), (0.44 +/- 0.12) and (0.37 +/- 0.11). Both the mRNA and the protein levels of MMP-9 were inversely correlated with FEV1 % and FEV1/FVC% (r= -0.759, -0.756, -0.772, -0.725, respectively, P <0.01). TIMP-1 mRNA level was inversely correlated with FEV1% and FEV1/FVC% (r = -0.675, -0.623, respectively P <0.01). Negative correlations were also noted between ICAM-1 expressions (both mRNA and protein) and FEV1% or FEV1/FVC% (r = -0.580, -0.531, -0.739, -0.756, respectively P <0.01). Interestingly, the mRNA expression of TIMP-1, MMP-9 and ICAM-1 was positively correlated (r = 0.576, 0.524, P < 0.01), while the protein levels of MMP-9 and ICAM-1 were positively correlated (r = 0.964, P <0.01).


CONCLUSIONS
There was a significant correlation between over-expression of ICAM-1 and TIMP-land MMP-9 in lung tissues from COPD patients. Over-expressions of ICAM-1 in the lung may result in accumulation of inflammatory cells releasing certain inflammatory factors that could destroy the normal lung structure. In addition, highly expressed TIMP-1 and MMP-9 in lung tissues may also contribute to the destruction and reconstitution of the bronchial or/and alveolar wall, which is likely to play a major role in airway obstruction.
Kong
Ying-Jun
YJ
Department of Respiratory Medicine, the First Clinical College of Harbin Medical University, Harbin 150001, China.
Sun
Wen-Xue
WX
Zhang
Yi-Mei
YM
Shi
Yu-Zhi
YZ
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D012907:Smoking; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*
D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D018799:Intercellular Adhesion Molecule-1; D020780:Matrix Metalloproteinase 9