RATIONALE: 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 to 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 analysis. Protein networks that model the
protein interactions in the BALF were generated using Ingenuity Pathway Analysis. 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. CONCLUSION:
Proteomics and protein network analyses reveal 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.