TY - JOUR
T1 - Quantitative intact proteomics investigations of alveolar macrophages in sarcoidosis
AU - Silva, Ernesto
AU - Souchelnytskyi, Serhiy
AU - Kasuga, Kie
AU - Eklund, Anders
AU - Grunewald, Johan
AU - Wheelock, Åsa M.
PY - 2013/6/1
Y1 - 2013/6/1
N2 - 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 Fcc-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. Copyright
AB - 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 Fcc-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. Copyright
KW - Differential gel electrophoresis
KW - Endocytosis
KW - Mass spectrometry
KW - Multivariate analysis
KW - Phagocytosis
KW - Proteomics
UR - http://www.scopus.com/inward/record.url?scp=84878810635&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84878810635&partnerID=8YFLogxK
U2 - 10.1183/09031936.00178111
DO - 10.1183/09031936.00178111
M3 - Article
C2 - 23060632
AN - SCOPUS:84878810635
VL - 41
SP - 1331
EP - 1339
JO - Scandinavian Journal of Respiratory Diseases
JF - Scandinavian Journal of Respiratory Diseases
SN - 0903-1936
IS - 6
ER -