Prolyl Endopeptidase (PE): An important enzyme involved in the development of lung emphysema?

Rationale: There is increasing evidence that the neutrophil chemoattractant PGP, derived from the breakdown of the extracellular matrix, plays an important role in neutrophil recruitment to the lung. PGP formation is a multistep process involving neutrophils, MMPs and PE. In this study, this cascade of events leading to lung emphysema was investigated. Methods: A/J mice were exposed whole body to cigarette smoke during 5 months. At different time points the animals were sacrificed and bronchoalveolar lavage fluid (BALF) and lung tissue were collected. BALF cell counts and differentiation were analyzed. MMP-9 and PE levels were measured in the BALF by western blotting and ELISA. PE was detected in the lung tissue by immunohistology and PGP was measured using Mass spectrometry. Lung tissue degradation was assessed by measuring the mean linear intercept. Results: A neutrophil influx in the BALF was induced by cigarette smoke exposure. MMP-9, PE and PGP levels were increased in BALF of cigarette smoke exposed mice. Interestingly, PE was highly expressed in different cell types in lung tissue of cigarette smoke exposed animals. Conclusion: Together with MMPs, PE may play an important role in the formation of PGP and thus in the pathophysiology of lung emphysema, which could open new avenues for the treatment of this disease. Funded by: TIPharma: T1-103; CXC chemokine receptors: potential targets for chronic inflammatory diseases.