Quantitative intact proteomics investigations of alveolar macrophages in sarcoidosis

Abstract

Alveolar macrophages are important for granuloma formation, which is the histological hallmark in sarcoidosis. Their function as antigen-presenting cells in sarcoidosis is also believed to be relevant to the outcome of disease, resulting either in remission or a prolonged chronic inflammation in the lungs. Our aim was to study alterations in the expression levels of the soluble proteome of alveolar macrophages in pulmonary sarcoidosis as compared with healthy controls, with the goal of identifying specific proteins and pathways important for the mechanisms of disease and/or disease phenotype. Quantitative proteomics approach using two-dimensional difference gel electrophoresis coupled to mass spectrometry was applied. Data was evaluated using multivariate modelling and pathway analyses. 69 protein spots were found to be significantly altered between sarcoidosis and healthy controls. Among these, 25 unique proteins were identified. Several of the identified proteins were related to key alveolar macrophage functionality, including the Fcγ-mediated phagocytosis and clathrin-mediated endocytosis pathways. Global proteomics analysis provided identification of alterations of a subset of proteins not previously reported in sarcoidosis. These alterations primarily affect biological pathways related to phagocytic macrophage functionality. These findings provide important insights into the role of macrophages in sarcoidosis pathogenesis.