+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

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

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

Respiratory Research 2(5): 300-305

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. 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. 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. The current study demonstrates that interactions between monocytes and fibroblasts can mediate tissue remodeling.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 045561214

Download citation: RISBibTeXText

PMID: 11686900

DOI: 10.1186/rr73

Related references

Matrix metalloproteinases (MMPs), the main extracellular matrix (ECM) enzymes in collagen degradation, as a target for anticancer drugs. Journal of Enzyme Inhibition and Medicinal Chemistry 31(Sup1): 177-183, 2016

Endothelin 1 en1 does not directly stimulate human neutrophil hn elastase degradation of extracellular matrix ecm. FASEB Journal 6(4): A1043, 1992

Characterization of total and active matrix metalloproteinases-1, -3, and -13 synthesized and secreted by anterior cruciate ligament fibroblasts in three-dimensional collagen gels. Tissue Engineering. Part A 20(1-2): 171-177, 2014

Respective contribution of neutrophil elastase and matrix metalloproteinase 9 in the degradation of BP180 (type XVII collagen) in human bullous pemphigoid. Journal of Investigative Dermatology 117(5): 1091-1096, 2001

Extracellular matrix interactions during the in vivo degradation of collagen membranes in the rat skin: immunohistochemical distribution of collagen types IV, V, and VI. Journal of Biomedical Materials Research 29(9): 1121-1127, 1995

Ovine forestomach matrix biomaterial is a broad spectrum inhibitor of matrix metalloproteinases and neutrophil elastase. International Wound Journal 11(4): 392-397, 2015

Smoking and matrix metalloproteinases, neutrophil elastase and myeloperoxidase in chronic periodontitis. Oral Diseases 17(1): 68-76, 2011

Matrix metalloproteinases (MMP-8 and -9) and neutrophil elastase in gingival crevicular fluid of cyclosporin-treated patients. Journal of Periodontology 72(3): 354-360, 2001

Human neutrophil elastase augments fibroblast-mediated contraction of released collagen gels. American Journal of Respiratory and Critical Care Medicine 159(4 Pt 1): 1138-1146, 1999

Quantification of human neutrophil motility in three-dimensional collagen gels. Effect of collagen concentration. Biophysical Journal 61(2): 306-315, 1992

Serum and salivary matrix metalloproteinases, neutrophil elastase, myeloperoxidase in patients with chronic or aggressive periodontitis. Inflammation 37(5): 1771-1778, 2015

Sequestration of matrix metalloproteinases -1, -3 and -8 by the alpha2-chain of collagen VI in the extracellular matrix. Naunyn-Schmiedeberg's Archives of Pharmacology 362(4-5 Supplement): R19, 2000

Matrix metalloproteinases -1, -3 and -8 are exclusively bound by the alpha2-chain of collagen VI in the liver extracellular matrix. Journal of Hepatology 32(Supplement 2): 64, 2000

A role for extracellular matrix degradation and matrix metalloproteinases in senile dementia?. Acta Neuropathologica. 87(3): 308-312, 1994

Matrix metalloproteinases produced by IL-2 activated natural killer cells and extracellular matrix degradation. Natural Immunity 15(4): 187, 1996-, 1997