Human neutrophil elastase augments fibroblast-mediated contraction of released collagen gels

In the present study, we tested the hypothesis that neutrophil elastase (NE ) might mediate remodeling of extracellular matrix by affecting fibroblast- mediated contraction of three-dimensional collagen gels. Human lung Fibrobl asts were cast into type I collagen gels containing NE. After gelation, the gels were released into medium and the area was measured by image analyzer . NE augmented gel contraction (p < 0.001). This was not due to cell prolif eration or to degradation to soluble collagen fragments because the amounts of DNA and hydroxyproline were not altered, alpha(1)-Protease inhibitor an d the synthetic inhibitor of NE, 1-680,833, when added in sufficient amount to inhibit free elastase activity, blocked the contraction induced by NE. Furthermore, neutrophil granulocytes (PMN) in coculture, as well as conditi oned media from PMN, resulted in an increased contractility (p < 0.001 for both). Bronchoalveolar lavage fluid (BALF) from patients with increased PMN in their lower respiratory tract and free elastase activity had augmentive activity for gel contraction which could be partially blocked by the Inhib itors. We conclude that NE augments fibroblast-mediated contraction of coll agen gels. The findings support the nation that products secreted by PMN in Inflammatory disorders may lead to rearrangement of extracellular matrix a nd could subsequently lead to tissue dysfunction.