Proteomics analysis of alveolar macrophages in sarcoidosis patients
Background: Sarcoidosis is a severe and potentially fatal inflammatory disease that can affect almost any organs in the body. Although 90% of patients show symptoms in the lungs, the disease can attack heart, eye, central nervous system, liver and kidney. The acute form of sarcoidosis is known as Löfgren's syndrome and remits spontaneously in 75%-85% of the cases in within 2 years. Failure of regression within two years is considered to predict a chronic course. Sarcoidosis was once though rare; it is now known to be common and affects people worldwide. The cause of the disease is unknown and at the present there is no cure. The classical feature of sarcoidosis is the formation of granuloma: a sort of clump of inflammatory cells that develops in the organ tissue (Fig. 1).
Fig. 1. Granulomas in lung tissue
When too many granulomas develop in an organ, they can interfere with its normal function. Granulomas are formed by epitheliod cells originated from monocytes/macrophages and by T-lymphocytes. Understanding the role of alveolar macrophages (AMs) in the pathogenesis of sarcoidosis is only at the beginning and especially their function in granuloma formation and secondary fibrosis needs further elucidation.
The hypothesis of our project is that AMs act differently in acute and chronic sarcoidosis. This is based on the observation that the composition of the inflammatory mediators in the bronchoalveolar lavages is dissimilar in acute and in chronic patients. The exposure to different mediators may influence the behaviour of AMs, which may be read out by protein expression profiling showing diverse protein profiles in acute and chronic state of the disease.
Approach: The overall changes at protein levels between 2 groups of patients are detected by the analysis of protein profiles obtained by 2D-dimensional gel electrophoresis (2D-gel). In Fig 2 the protein profiles of non-sarcoid controls, Löfgren's syndrome and chronic patients are shown.
Fig. 2: Protein profiles of the analyzed group
of patients
At the moment we have found 24 and 19 protein spots that are differentially (up-down regulated) in acute and chronic patients respectively. The differentially expressed proteins are identified by ESI-Q-TOF mass spectrometry. In order to understand the biological relevance of the identified proteins we applied data mining tools (SAM GoMiner database). The results suggest that AM of acute patients are characterized by an enhanced rate apoptosis caused by an increased oxidative stress.
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