Centre for Translational Inflammation Research, University of Birmingham Research Laboratories, Queen Elizabeth Hospital, Birmingham, UK.
Eur Respir J. 2013 May;41(5):1042-50. doi: 10.1183/09031936.00089712. Epub 2012 Aug 30.
Chronic obstructive pulmonary disease (COPD) is associated with tissue damage believed to result from an imbalance between serine proteinases and their inhibitors. Although the role of neutrophil elastase (NE) has been studied, it is likely that other proteinases play a role. The importance of proteinase 3 (PR3) has not been established, as specific substrates have only recently been available. We studied clinically stable subjects with either alpha-1-antitrypsin (A1AT) deficiency or usual COPD with chronic bronchitis. Sol phase sputum was analysed for PR3 activity and concentration, NE activity and concentration, concentrations of airway inhibitors (A1AT, secretory leukoproteinase inhibitor and elafin) and markers of neutrophilic inflammation. 12 patients were also studied during exacerbations. PR3 activity was present in most sputum samples and greater than NE activity (which was largely undetectable) in both subject groups (A1AT deficiency median PR3 128 nM, interquartile range (IQR) 33-558 nM; NE 0 nM, IQR 0-0 nM; p=0.0043; COPD PR3 22 nM, IQR 0-103 nM; NE 0 nM, IQR 0-0 nM; p=0.015). PR3 activity was greater during exacerbations than in the stable state (p=0.037) and correlated with markers of neutrophilic inflammation. The regular identification of PR3 activity in sputum from stable subjects with A1AT deficiency or usual COPD suggests it may play a greater role in the pathophysiology than previously thought.
慢性阻塞性肺疾病（COPD）与组织损伤有关，这种损伤被认为是由于丝氨酸蛋白酶及其抑制剂之间的失衡所致。虽然已经研究了中性粒细胞弹性蛋白酶（NE）的作用，但其他蛋白酶可能也发挥了作用。蛋白酶 3（PR3）的重要性尚未确定，因为最近才出现了特定的底物。我们研究了具有α-1-抗胰蛋白酶（A1AT）缺乏症或通常伴有慢性支气管炎的 COPD 的临床稳定患者。对溶胶相痰液进行 PR3 活性和浓度、NE 活性和浓度、气道抑制剂（A1AT、分泌型白细胞蛋白酶抑制剂和 Elafin）浓度以及中性粒细胞炎症标志物的分析。还对 12 名患者在病情加重期间进行了研究。PR3 活性存在于大多数痰液样本中，并且在两个患者组中的活性均大于 NE 活性（后者主要无法检测到）（A1AT 缺乏症患者的中位数 PR3 活性为 128 nM，四分位距（IQR）为 33-558 nM；NE 活性为 0 nM，IQR 为 0-0 nM；p=0.0043；COPD 患者的 PR3 活性为 22 nM，IQR 为 0-103 nM；NE 活性为 0 nM，IQR 为 0-0 nM；p=0.015）。PR3 活性在病情加重期间大于稳定状态（p=0.037），并且与中性粒细胞炎症标志物相关。在 A1AT 缺乏症或通常患有 COPD 的稳定患者的痰液中经常检测到 PR3 活性，这表明它在病理生理学中的作用可能比以前认为的更大。
