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

C. Magnus Sköld, Xiang-de Liu, Takeshi Umino, Yunkui Zhu, Yoshihiro Ohkuni, Debra Romberger, John R. Spurzem, Arthur J. Heires, Stephen I. Rennard

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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 fibroblasts 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 proliferation or to degradation to soluble collagen fragments because the amounts of DNA and hydroxyproline were not altered. α1-Protease inhibitor and the synthetic inhibitor of NE, L-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 conditioned 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 inhibitors. We conclude that NE augments fibroblast-mediated contraction of collagen gels. The findings support the notion that products secreted by PMN in inflammatory disorders may lead to rearrangement of extracellular matrix and could subsequently lead to tissue dysfunction.

Original languageEnglish (US)
Pages (from-to)1138-1146
Number of pages9
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume159
Issue number4 I
DOIs
StatePublished - Jan 1 1999

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Leukocyte Elastase
Collagen
Fibroblasts
Gels
Pancreatic Elastase
L 680833
Extracellular Matrix
Secretory Proteinase Inhibitory Proteins
Hydroxyproline
Bronchoalveolar Lavage Fluid
Conditioned Culture Medium
Coculture Techniques
Collagen Type I
Protease Inhibitors
Granulocytes
Respiratory System
Neutrophils
Cell Proliferation
Lung
DNA

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Human neutrophil elastase augments fibroblast-mediated contraction of released collagen gels. / Sköld, C. Magnus; Liu, Xiang-de; Umino, Takeshi; Zhu, Yunkui; Ohkuni, Yoshihiro; Romberger, Debra; Spurzem, John R.; Heires, Arthur J.; Rennard, Stephen I.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 159, No. 4 I, 01.01.1999, p. 1138-1146.

Research output: Contribution to journalArticle

Sköld, C. Magnus ; Liu, Xiang-de ; Umino, Takeshi ; Zhu, Yunkui ; Ohkuni, Yoshihiro ; Romberger, Debra ; Spurzem, John R. ; Heires, Arthur J. ; Rennard, Stephen I. / Human neutrophil elastase augments fibroblast-mediated contraction of released collagen gels. In: American Journal of Respiratory and Critical Care Medicine. 1999 ; Vol. 159, No. 4 I. pp. 1138-1146.
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