Proteome analysis of bronchoalveolar lavage in pulmonary langerhans cell histiocytosis.

摘要

Background: Pulmonary Langerhans-cell histiocytosis (PLCH) is a rare interstitial lung disease characterized by\udclusters of Langerhans cells, organized in granulomas, in the walls of distal bronchioles. It is a diffuse lung disease\udrelated to tobacco smoking but otherwise of unknown etiopathogenesis.\udMethods: In this study we used a proteomic approach to analyze BAL protein composition of patients with PLCH\udand of healthy smoker and non-smoker controls to obtain insights into the pathogenetic mechanisms of the\uddisease, to study the effect of cigarette smoking on susceptibility to PLCH and to identify potential new\udbiomarkers.\udResults: Two-dimensional electrophoresis and image analysis revealed proteins that were differently expressed\ud(quantitatively and qualitatively) in the three groups of subjects. The proteins were identified by mass spectrometry\udand have various functions (antioxidant, proinflammatory, antiprotease) and origins (plasma, locally produced, etc.).\udMany, such as protease inhibitors (human serpin B3) and antioxidant proteins (glutathione peroxidase and\udthioredoxin) are already linked to PLCH pathogenesis, whereas other proteins have never been associated with the\uddisease. Interestingly, numerous proteolytic fragments of plasma proteins (including kininogen-1 N fragments and\udhaptoglobin) were also identified and suggest increased proteolytic activity in this inflammatory lung disease.\udDifferences in protein expression were found between the three groups and confirmed by Principal Component\udAnalysis (PCA).\udConclusion: Analysis of BAL proteomes of PLCH patients and of smoker and non-smoker controls also proved to\udbe useful for researching the pathogenetic mechanisms and for identifying biomarkers of this rare diffuse lung\uddisease.