Proteolytic cleavage of elafin by 20S proteasome may contribute to inflammation in acute lung injury

Aoife Kerrin, Sinéad Weldon, Allen Hung-Kang Chung, Thelma Craig, A John Simpson, Cecilia M O'Kane, Danny Francis McAuley, Clifford C Taggart

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract


RATIONALE:
We hypothesise that elafin levels in acute lung injury (ALI) decrease over time due, in part, to proteolytic degradation as observed in other lung diseases.
OBJECTIVES:
The aim of this study was to characterise temporal changes in elafin concentration in patients with ALI and to evaluate whether a decrease in elafin levels is due to elevated protease activity.
METHODS:
Bronchoalveolar lavage fluid (BALF) was obtained from patients with ALI within 48 h of onset of ALI (day 0), at day 3 and at day 7. Elafin levels were quantified by ELISA. Elafin susceptibility to proteolytic cleavage by ALI BALF was assessed by Western blot and by high-performance liquid chromatography-mass spectrometry.
MEASUREMENTS AND MAIN RESULTS:
Elafin levels were found to be significantly increased at the onset of ALI compared with healthy volunteers and fell significantly by day 7 compared with day 0. In contrast, levels of secretory leukocyte protease inhibitor did not decrease over time. This decrease in elafin was due to cleavage by the 20S proteasome which was significantly increased in ALI BALF. Incubation of ALI BALF with the proteasome inhibitor epoxomicin confirmed that 20S proteasome protease activity was responsible for proteolytic cleavage of elafin, resulting in diminished anti-elastase activity. In addition, free neutrophil elastase activity significantly increased in ALI BALF from day 0 to day 7.
CONCLUSIONS:
Elafin concentrations fall within the pulmonary compartment over the course of ALI as a result of proteolytic degradation. This loss of elafin may predispose people, in part, to excessive inflammation in ALI.
Original languageEnglish
Pages (from-to)315-321
Number of pages7
JournalThorax
Volume68
Issue number4
Early online date14 Dec 2012
DOIs
Publication statusPublished - Apr 2013

Keywords

  • Acute Lung Injury
  • Blotting, Western
  • Bronchoalveolar Lavage Fluid
  • Elafin
  • Electrophoresis, Polyacrylamide Gel
  • Humans
  • Proteasome Endopeptidase Complex
  • Proteolysis
  • Recombinant Proteins
  • Secretory Leukocyte Peptidase Inhibitor

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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