Proteomic and computational analysis of bronchoalveolar proteins during the course of the acute respiratory distress syndrome.
BACKGROUND
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.


OBJECTIVE
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.


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.
Chang
Dong W
DW
Medical Research Service, VA Puget Sound Healthcare System, Seattle, Washington 98108, USA.
Hayashi
Shinichi
S
Gharib
Sina A
SA
Vaisar
Tomas
T
King
S Trevor
ST
Tsuchiya
Mitsuhiro
M
Ruzinski
John T
JT
Park
David R
DR
Matute-Bello
Gustavo
G
Wurfel
Mark M
MM
Bumgarner
Roger
R
Heinecke
Jay W
JW
Martin
Thomas R
TR
D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D040901:Proteomics; D012128:Respiratory Distress Syndrome / Q000503:physiopathology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D049490:Systems Biology