Bchir Sarra, Nasr Hela Ben, Bouchet Sandrine, Benzarti Mohamed, Garrouch Abdelhamid, Tabka Zouhair, Susin Santos, Chahed Karim, Bauvois Brigitte
Unité de recherche UR12ES06, Physiologie de l'Exercice et Physiopathologie de l'Intégré au Moléculaire, Biologie, Médecine et Santé, Faculté de Médecine de Sousse, Université de Sousse, Sousse, Tunisia.
Institut Supérieur de Biotechnologie de Monastir, Université de Monastir, Monastir, Tunisia.
J Cell Mol Med. 2017 Jul;21(7):1280-1291. doi: 10.1111/jcmm.13057. Epub 2016 Dec 22.
A growing body of evidence points towards smoking-related phenotypic differences in chronic obstructive pulmonary disease (COPD). As COPD is associated with systemic inflammation, we determined whether smoking status is related to serum levels of matrix metalloproteinase-9 (pro- and active MMP-9), neutrophil gelatinase-associated lipocalin (NGAL) and the proMMP-9/NGAL complex in patients with COPD. Serum samples were collected in 100 stable-phase COPD patients (82 smokers, 18 never-smokers) and 28 healthy adults (21 smokers, 7 never-smokers). Serum levels of studied factors were measured in ELISA. Our data provide the first evidence of simultaneously elevated serum levels of MMP-9, NGAL and proMMP-9/NGAL in COPD smokers. While the triad discriminated between smokers and non-smokers in the COPD group, MMP-9 and proMMP-9/NGAL (but not NGAL) discriminated between smokers with and without COPD. Adjustment for age and smoking pack-years did not alter the findings. Serum MMP-9, NGAL and proMMP-9/NGAL levels were not correlated with the GOLD stage or FEV1 decline. Furthermore, serum levels of neutrophil elastase (NE) and MMP-3 (but not of IL-6 and MMP-12) were also higher in COPD smokers than in healthy smokers before and after adjustment for age and pack-years. Among COPD smokers, levels of MMP-9, NGAL and proMMP-9/NGAL were positively correlated with NE (P < 0.0001) but not with the remaining factors. Gelatin zymography detected proMMP-9 in serum samples of healthy and COPD smoking groups. Our results suggest that associated serum levels of proMMP-9, NGAL, proMMP-9/NGAL and NE may reflect the state of systemic inflammation in COPD related to cigarette smoking.
越来越多的证据表明，慢性阻塞性肺疾病（COPD）存在与吸烟相关的表型差异。由于COPD与全身炎症相关，我们研究了吸烟状态是否与COPD患者血清中的基质金属蛋白酶-9（前体和活性MMP-9）、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）以及前体MMP-9/NGAL复合物水平有关。收集了100例稳定期COPD患者（82例吸烟者，18例从不吸烟者）和28例健康成年人（21例吸烟者，7例从不吸烟者）的血清样本。采用酶联免疫吸附测定法（ELISA）检测所研究因子的血清水平。我们的数据首次证明，COPD吸烟者血清中MMP-9、NGAL和前体MMP-9/NGAL水平同时升高。虽然这三者在COPD组中区分了吸烟者和非吸烟者，但MMP-9和前体MMP-9/NGAL（而非NGAL）区分了患有和未患COPD的吸烟者。对年龄和吸烟包年数进行校正后，结果未改变。血清MMP-9、NGAL和前体MMP-9/NGAL水平与慢性阻塞性肺疾病全球倡议（GOLD）分级或第一秒用力呼气容积（FEV1）下降无关。此外，在校正年龄和吸烟包年数前后，COPD吸烟者血清中性粒细胞弹性蛋白酶（NE）和MMP-3水平（而非白细胞介素-6和MMP-12水平）也高于健康吸烟者。在COPD吸烟者中，MMP-9、NGAL和前体MMP-9/NGAL水平与NE呈正相关（P<0.0001），但与其他因素无关。明胶酶谱法在健康和COPD吸烟组的血清样本中检测到前体MMP-9。我们的结果表明，血清中前体MMP-9、NGAL、前体MMP-9/NGAL和NE的相关水平可能反映了与吸烟相关的COPD全身炎症状态。
