Published ahead of print on July 24, 2008, doi:10.1164/rccm.200712-1895OC
© 2008 American Thoracic Society doi: 10.1164/rccm.200712-1895OC
Proteomic and Computational Analysis of Bronchoalveolar Proteins during the Course of the Acute Respiratory Distress Syndrome1 Medical Research Service of the VA Puget Sound Healthcare System, Seattle, Washington; Divisions of 2 Pulmonary and Critical Care Medicine and 3 Endocrinology and Metabolism, Department of Medicine; and 4 Department of Microbiology; 5 Center for Lung Biology; and 6 Fred Hutchinson Cancer Research Institute, University of Washington, Seattle, Washington Correspondence and requests for reprints should be addressed to Thomas R. Martin, M.D., Pulmonary Research Laboratories, VA Puget Sound Health Care System, 1660 S. Columbian Way, 151L Seattle, WA 98108. E-mail: trmartin{at}u.washington.edu Rationale: Acute lung injury causes complex changes in protein expression in the lungs. Whereas most prior studies focused on single proteins, newer methods allowing the simultaneous study of many proteins could lead to a better understanding of pathogenesis and new targets for treatment. Objectives: The purpose of this study was to examine the changes in protein expression in the bronchoalveolar lavage fluid (BALF) of patients during the course of the acute respiratory distress syndrome (ARDS). Methods: Using two-dimensional difference gel electrophoresis (DIGE), the expression of proteins in the BALF from patients on Days 1 (n = 7), 3 (n = 8), and 7 (n = 5) of ARDS were compared with findings in normal volunteers (n = 9). The patterns of protein expression were analyzed using principal component analysis (PCA). Biological processes that were enriched in the BALF proteins of patients with ARDS were identified using Gene Ontology (GO) analysis. Protein networks that model the protein interactions in the BALF were generated using Ingenuity Pathway Analysis. Measurements and Main Results: An average of 991 protein spots were detected using DIGE. Of these, 80 protein spots, representing 37 unique proteins in all of the fluids, were identified using mass spectrometry. PCA confirmed important differences between the proteins in the ARDS and normal samples. GO analysis showed that these differences are due to the enrichment of proteins involved in inflammation, infection, and injury. The protein network analysis showed that the protein interactions in ARDS are complex and redundant, and revealed unexpected central components in the protein networks. Conclusions: Proteomics and protein network analysis reveals the complex nature of lung protein interactions in ARDS. The results provide new insights about protein networks in injured lungs, and identify novel mediators that are likely to be involved in the pathogenesis and progression of acute lung injury.
Key Words: acute respiratory distress syndrome • acute lung injury • proteomic analysis • bronchoalveolar lavage • 2D gel electrophoresis
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