Impaired SERPIN-Protease Balance in the Peripheral Lungs of Stable COPD Patients

The protease-antiprotease balance is involved in many biological processes, including blood coagulation, tissue remodeling, inflammation and immune responses. The aim of this study is to determine the balance between SERPINs and some related proteases in the lungs of stable COPD patients. In this cross-sectional study, the expression and localization of human SERPINs (anti-proteases) and some related proteases were measured in the lung parenchyma of mild-moderate COPD (MCOPD, n = 13) patients, control smokers (CS, n = 14) and control nonsmokers (CNS, n = 12) using transcriptome analysis, immunohistochemistry, and ELISA tests. Peripheral lung transcriptomic data showed increased mRNA levels of tissue plasminogen activator (tPA), cathepsin-L and caspase-1 as well as increased SERPINs A6, B3, B5, B11, B13 in the COPD group compared to the CNS group. At the protein level, IHC analysis showed that tPA and cathepsin-L increased in the bronchiolar epithelium and alveolar septa of the CS and COPD groups compared to the CNS group, as well as SERPINB5 and B13 in the alveolar macrophages and alveolar septa of the CS and COPD groups compared to the CNS group. SERPINA6 was shown to be decreased in the bronchiolar epithelium, bronchiolar lamina propria, and alveolar septa of the CS and COPD groups compared to the CNS group and was positively correlated with lung function. SERPINB3 was decreased in the alveolar septa of the CS group compared to the CNS group. The ELISA tests showed that in the total lung extracts, decreased levels of SERPINA6 and increased caspase-1 were shown in the COPD group compared to the CNS or both control groups, respectively. These data show an imbalance, at the protein level, of SERPINs and some related proteases in the lungs of the CS and stable COPD groups. These alterations may play a role in damaging the lung parenchyma of susceptible COPD patients.