Type

Journal Article

Authors

Noel G McElvaney
Clifford C Taggart
Shane J O'Neill
Rodney L Levine
Catherine M Greene
Sinéad Weldon
Paul McNally
Marcus W Butler
Nicolas Guyot

Subjects

Microbiology

Topics
pseudomonas aeruginosa humans recombinant proteins metabolism cross linking reagents cystic fibrosis pharmacology lipopolysaccharides protein structure tertiary elafin protein binding leukocyte elastase fibronectins chemistry pseudomonas infections microbiology dose response relationship drug models biological sputum enzymology

Elafin, an elastase-specific inhibitor, is cleaved by its cognate enzyme neutrophil elastase in sputum from individuals with cystic fibrosis. (2008)

Abstract Elafin is a neutrophil serine protease inhibitor expressed in lung and displaying anti-inflammatory and anti-bacterial properties. Previous studies demonstrated that some innate host defense molecules of the cystic fibrosis (CF) and chronic obstructive pulmonary disease airways are impaired due to increased proteolytic degradation observed during lung inflammation. In light of these findings, we thus focused on the status of elafin in CF lung. We showed in the present study that elafin is cleaved in sputum from individuals with CF. Pseudomonas aeruginosa-positive CF sputum, which was found to contain lower elafin levels and higher neutrophil elastase (NE) activity compared with P. aeruginosa-negative samples, was particularly effective in cleaving recombinant elafin. NE plays a pivotal role in the process as only NE inhibitors are able to inhibit elafin degradation. Further in vitro studies demonstrated that incubation of recombinant elafin with excess of NE leads to the rapid cleavage of the inhibitor. Two cleavage sites were identified at the N-terminal extremity of elafin (Val-5-Lys-6 and Val-9-Ser-10). Interestingly, purified fragments of the inhibitor (Lys-6-Gln-57 and Ser-10-Gln-57) were shown to still be active for inhibiting NE. However, NE in excess was shown to strongly diminish the ability of elafin to bind lipopolysaccharide (LPS) and its capacity to be immobilized by transglutamination. In conclusion, this study provides evidence that elafin is cleaved by its cognate enzyme NE present at excessive concentration in CF sputum and that P. aeruginosa infection promotes this effect. Such cleavage may have repercussions on the innate immune function of elafin.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Noel G McElvaney, Clifford C Taggart, Shane J O'Neill, Rodney L Levine, Catherine M Greene, Sinéad Weldon, Paul McNally, Marcus W Butler, Nicolas Guyot

Experts in our system

1
Noel G McElvaney
Royal College of Surgeons in Ireland
Total Publications: 194
 
2
Clifford C Taggart
Royal College of Surgeons in Ireland
Total Publications: 54
 
3
Shane J O'Neill
Royal College of Surgeons in Ireland
Total Publications: 84
 
4
Catherine M Greene
Royal College of Surgeons in Ireland
Total Publications: 150
 
5
Sinéad Weldon
Royal College of Surgeons in Ireland
Total Publications: 9
 
6
Paul McNally
Royal College of Surgeons in Ireland
Total Publications: 26
 
7
Marcus W Butler
Royal College of Surgeons in Ireland
Total Publications: 9