Collaborative interactions between neutrophil elastase and metalloproteinases in extracellular matrix degradation in three dimensional collagen gels

Yunkui Zhu, Xiang-de Liu, C. Magnus Sköld, Hangjun Wang, Tadashi Kohyama, Fu Qiang Wen, Ronald F. Ertl, Stephen I. Rennard

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Background: Extended culture of monocytes and fibroblasts in three-dimensional collagen gels leads to degradation of the gels (see linked study in this issue, "Fibroblasts and monocytes contract and degrade three-dimensional collagen gels in extended co-culture"). The current study, therefore, was designed to evaluate production of matrix-degrading metalloproteinases by these cells in co-culture and to determine if neutrophil elastase could collaborate in the activation of these enzymes. Since co-cultures produce prostaglandin E2 (PGE2), the role of PGE2 in this process was also evaluated. Methods: Blood monocytes from healthy donors and human fetal lung fibroblasts were cast into type I collagen gels and maintained in floating cultures for three weeks. Matrix metalloproteinases (MMPs) were assessed by gelatin zymography (MMPs 2 and 9) and immunoblotting (MMPs 1 and 3). The role of PGE2 was explored by direct quantification, and by the addition of exogenous indomethacin and/or PGE2. Results: Gelatin zymography and immunoblots revealed that MMPs 1, 2, 3 and 9 were induced by co-cultures of fibroblasts and monocytes. Neutrophil elastase added to the medium resulted in marked conversion of latent MMPs to lower molecular weight forms consistent with active MMPs, and was associated with augmentation of both contraction and degradation (P<0.01). PGE2 appeared to decrease both MMP production and activation. Conclusion: The current study demonstrates that interactions between monocytes and fibroblasts can mediate tissue remodeling.

Original languageEnglish (US)
Pages (from-to)300-305
Number of pages6
JournalRespiratory Research
Volume2
Issue number5
DOIs
StatePublished - Dec 1 2001

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Leukocyte Elastase
Metalloproteases
Matrix Metalloproteinases
Dinoprostone
Extracellular Matrix
Monocytes
Coculture Techniques
Collagen
Fibroblasts
Gels
Matrix Metalloproteinase 1
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Gelatin
Matrix Metalloproteinase 3
Enzyme Activation
Collagen Type I
Immunoblotting
Indomethacin
Molecular Weight

Keywords

  • Collagen degradation
  • Lung fibroblasts
  • Metalloproteinases
  • Monocytes
  • Prostaglandin E

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Collaborative interactions between neutrophil elastase and metalloproteinases in extracellular matrix degradation in three dimensional collagen gels. / Zhu, Yunkui; Liu, Xiang-de; Sköld, C. Magnus; Wang, Hangjun; Kohyama, Tadashi; Wen, Fu Qiang; Ertl, Ronald F.; Rennard, Stephen I.

In: Respiratory Research, Vol. 2, No. 5, 01.12.2001, p. 300-305.

Research output: Contribution to journalArticle

Zhu, Yunkui ; Liu, Xiang-de ; Sköld, C. Magnus ; Wang, Hangjun ; Kohyama, Tadashi ; Wen, Fu Qiang ; Ertl, Ronald F. ; Rennard, Stephen I. / Collaborative interactions between neutrophil elastase and metalloproteinases in extracellular matrix degradation in three dimensional collagen gels. In: Respiratory Research. 2001 ; Vol. 2, No. 5. pp. 300-305.
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