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Distinct proteasome subpopulations in the alveolar space of patients with the acute respiratory distress syndrome.

Authors: Sixt, SU  Alami, R  Hakenbeck, J  Adamzik, M  Kloss, A  Costabel, U  Jungblut, PR  Dahlmann, B  Peters, J 
Citation: Sixt SU, etal., Mediators Inflamm. 2012;2012:204250. Epub 2012 Jan 29.
Pubmed: (View Article at PubMed) PMID:22363101
DOI: Full-text: DOI:10.1155/2012/204250

There is increasing evidence that proteasomes have a biological role in the extracellular alveolar space, but inflammation could change their composition. We tested whether immunoproteasome protein-containing subpopulations are present in the alveolar space of patients with lung inflammation evoking the acute respiratory distress syndrome (ARDS). Bronchoalveolar lavage (BAL) supernatants and cell pellet lysate from ARDS patients (n = 28) and healthy subjects (n = 10) were analyzed for the presence of immunoproteasome proteins (LMP2 and LMP7) and proteasome subtypes by western blot, chromatographic purification, and 2D-dimensional gelelectrophoresis. In all ARDS patients but not in healthy subjects LMP7 and LMP2 were observed in BAL supernatants. Proteasomes purified from pooled ARDS BAL supernatant showed an altered enzyme activity ratio. Chromatography revealed a distinct pattern with 7 proteasome subtype peaks in BAL supernatant of ARDS patients that differed from healthy subjects. Total proteasome concentration in BAL supernatant was increased in ARDS (971 ng/mL +/- 1116 versus 59 +/- 25; P < 0.001), and all fluorogenic substrates were hydrolyzed, albeit to a lesser extent, with inhibition by epoxomicin (P = 0.0001). Thus, we identified for the first time immunoproteasome proteins and a distinct proteasomal subtype pattern in the alveolar space of ARDS patients, presumably in response to inflammation.

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CRRD Object Information
CRRD ID: 6483444
Created: 2012-05-22
Species: All species
Last Modified: 2012-05-22
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.