RT Journal Article
SR Electronic
T1 Matrix metalloproteinases and tissue inhibitor of metalloproteinase-1 in sarcoidosis and IPF
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1220
OP 1227
DO 10.1183/09031936.02.00022302
VO 20
IS 5
A1 M.T. Henry
A1 K. McMahon
A1 A.J. Mackarel
A1 K. Prikk
A1 T. Sorsa
A1 P. Maisi
A1 R. Sepper
A1 M.X. FitzGerald
A1 C.M. O'Connor
YR 2002
UL http://erj.ersjournals.com/content/20/5/1220.abstract
AB The purpose of this study was to examine the role of interstitial collagenases, members of the family of matrix metalloproteinases, in the development of pulmonary fibrosis. The activity, levels and molecular forms of collagenases (matrix metalloproteinases (MMP)-1, -8 and -13), gelatinase B (MMP-9) and its main endogenous inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1) were assessed in bronchoalveolar lavage fluid (BALF) from patients with idiopathic pulmonary fibrosis (IPF) and sarcoidosis patients with varying degrees of pulmonary parenchymal involvement. Collagenase activity was elevated in IPF and group 3 sarcoidosis patients. A positive correlation between BALF collagenase activity and MMP-8 levels was also observed. Western immunoblotting revealed the presence of two isoforms of MMP-8 in patient samples; an 80 kD form representing latent enzyme from polymorphonuclear neutrophils and a 55 kD form representing the fibroblast-type proform. MMP-9 levels were also elevated in both IPF and group 3 sarcoidosis patients, while TIMP-1 levels remained normal, indicating a shift in the balance between the enzyme and inhibitor, favouring MMP-9. Matrix metalloproteinase-8 is the major contributor to the bronchoalveolar lavage fluid collagenase activity in the airways of patients with idiopathic pulmonary fibrosis and sarcoidosis and may initiate collagen destruction and remodelling leading to the development of pulmonary fibrosis. This work was supported by the EU Grant BMH4-CT96-0152 as part of the Biomed 2 EUROLUNG consortium.