Type

Journal Article

Authors

N G McElvaney
C C Taggart
S J O'Neill
M L Brantly
C M Greene
M P Rogan
P Geraghty

Subjects

Pharmacology

Topics
mmp2 protein human male monocytes matrix metalloproteinase 2 pneumonia leukocyte elastase alpha 1 antitrypsin pharmacology cathepsin b humans middle aged female administration inhalation chemistry alpha 1 antitrypsin deficiency metabolism bronchoalveolar lavage fluid serine proteinase inhibitors administration dosage

Alpha-1-antitrypsin aerosolised augmentation abrogates neutrophil elastase-induced expression of cathepsin B and matrix metalloprotease 2 in vivo and in vitro. (2008)

Abstract Neutrophil elastase (NE) activity is increased in lung diseases such as alpha(1)-antitrypsin (A1AT) deficiency and pneumonia. It has recently been shown to induce expression of cathepsin B and matrix metalloprotease 2 (MMP-2) in vitro and in a mouse model. It is postulated that increased cathepsin B and MMP-2 in acute and chronic lung diseases result from high levels of extracellular NE and that expression of these proteases could be inhibited by A1AT augmentation therapy. Cathepsin and MMP activities were assessed in bronchoalveolar lavage (BAL) fluid from patients with A1AT deficiency, pneumonia and control subjects. Macrophages were exposed to BAL fluid rich in free NE from patients with pneumonia following pretreatment with A1AT. MMP-2, cathepsin B, secretory leucoprotease inhibitor (SLPI) and lactoferrin levels were determined in BAL fluid from A1AT-deficient patients before and after aerosolisation of A1AT. BAL fluid from both patients with pneumonia and those with A1AT deficiency containing free NE had increased cathepsin B and MMP-2 activities compared with BAL fluid from healthy volunteers. The addition of A1AT to BAL fluid from patients with pneumonia greatly reduced NE-induced cathepsin B and MMP-2 expression in macrophages in vitro. A1AT augmentation therapy to A1AT-deficient individuals also reduced cathepsin B and MMP-2 activity in BAL fluid in vivo. Furthermore, A1AT-deficient patients had higher levels of SLPI and lactoferrin after A1AT augmentation therapy. These findings suggest a novel role for A1AT inhibition of NE-induced upregulation of MMP and cathepsin expression both in vitro and in vivo.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

N G McElvaney, C C Taggart, S J O'Neill, M L Brantly, C M Greene, M P Rogan, P Geraghty

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
Patrick Geraghty
Royal College of Surgeons in Ireland
Total Publications: 13