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Action of matrix metalloproteinases at restricted sites in colon anastomosis repair: an immunohistochemical and biochemical study

Agren, Magnus S.; Andersen, Thomas L.; Mirastschijski, Ursula; Syk, Ingvar LU ; Schiodt, Christine Bruun; Surve, Vikas; Lindebjerg, Jan and Delaisse, Jean-Marie (2006) In Surgery 140(1). p.72-82
Abstract
Background. Dehiscence of colon anastomosis is a common, serious and potentially life-threatening complication after colorectal operation. In experimental models, impaired biomechanic strength of colon anastomoses is preventable by general inhibitors of matrix metalloproteinases (MMPs) and associated with collagen loss, which indicates a possible link between MMP-mediated collagen degradation and dehiscence. The precise localization of collagen degradation within the anastomotic area and the specific MMPs responsible are unknown. Methods. We have analyzed distinct zones within anastomoses using a novel microdissection technique for collagen levels, collagenolytic activity exerted directly by endogenous proteinases, and MMP-8 and MMP-9... (More)
Background. Dehiscence of colon anastomosis is a common, serious and potentially life-threatening complication after colorectal operation. In experimental models, impaired biomechanic strength of colon anastomoses is preventable by general inhibitors of matrix metalloproteinases (MMPs) and associated with collagen loss, which indicates a possible link between MMP-mediated collagen degradation and dehiscence. The precise localization of collagen degradation within the anastomotic area and the specific MMPs responsible are unknown. Methods. We have analyzed distinct zones within anastomoses using a novel microdissection technique for collagen levels, collagenolytic activity exerted directly by endogenous proteinases, and MMP-8 and MMP-9 immunoreactivity and their collagenolytic activity. Results. The most pronounced collagen loss was observed in the suture-holding zone, showing a 29% drop compared with adjacent micro-areas of 3-day-old anastomoses. Only this specific tissue compartment underwent a dramatic and significant increase in collagenolysis, amounting to a loss of 10% of existing collagen molecules in 24 hours, and was abolished by metalloproteinase inhibitors. The tissue surrounding suture channels was heavily infiltrated with CD68-positive histiocytes that expressed MMP-8 and to a lesser extent MMP-9. The collagenolytic effect of the interstitial collagenase MMP-8 was synergistically potentiated by the gelatinase MMP-9 when added to colon biopsies incubated in vitro. Conclusions. The unique finding of this study was that the specific tissue holding the sutures of a colon anastomosis lost the most collagen presumably through induction and activation of multiple MMPs that may explain the beneficial effects of treatment with non-selective MMP antagonists. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Surgery
volume
140
issue
1
pages
72 - 82
publisher
Elsevier
external identifiers
  • wos:000239362100012
  • pmid:16857445
  • scopus:33745941622
ISSN
1532-7361
DOI
10.1016/j.surg.2005.12.013
language
English
LU publication?
yes
id
7cc46c35-992a-42f0-b5ba-3b57bd4e29b4 (old id 686343)
date added to LUP
2007-12-20 10:52:58
date last changed
2019-04-23 02:53:19
@article{7cc46c35-992a-42f0-b5ba-3b57bd4e29b4,
  abstract     = {Background. Dehiscence of colon anastomosis is a common, serious and potentially life-threatening complication after colorectal operation. In experimental models, impaired biomechanic strength of colon anastomoses is preventable by general inhibitors of matrix metalloproteinases (MMPs) and associated with collagen loss, which indicates a possible link between MMP-mediated collagen degradation and dehiscence. The precise localization of collagen degradation within the anastomotic area and the specific MMPs responsible are unknown. Methods. We have analyzed distinct zones within anastomoses using a novel microdissection technique for collagen levels, collagenolytic activity exerted directly by endogenous proteinases, and MMP-8 and MMP-9 immunoreactivity and their collagenolytic activity. Results. The most pronounced collagen loss was observed in the suture-holding zone, showing a 29% drop compared with adjacent micro-areas of 3-day-old anastomoses. Only this specific tissue compartment underwent a dramatic and significant increase in collagenolysis, amounting to a loss of 10% of existing collagen molecules in 24 hours, and was abolished by metalloproteinase inhibitors. The tissue surrounding suture channels was heavily infiltrated with CD68-positive histiocytes that expressed MMP-8 and to a lesser extent MMP-9. The collagenolytic effect of the interstitial collagenase MMP-8 was synergistically potentiated by the gelatinase MMP-9 when added to colon biopsies incubated in vitro. Conclusions. The unique finding of this study was that the specific tissue holding the sutures of a colon anastomosis lost the most collagen presumably through induction and activation of multiple MMPs that may explain the beneficial effects of treatment with non-selective MMP antagonists.},
  author       = {Agren, Magnus S. and Andersen, Thomas L. and Mirastschijski, Ursula and Syk, Ingvar and Schiodt, Christine Bruun and Surve, Vikas and Lindebjerg, Jan and Delaisse, Jean-Marie},
  issn         = {1532-7361},
  language     = {eng},
  number       = {1},
  pages        = {72--82},
  publisher    = {Elsevier},
  series       = {Surgery},
  title        = {Action of matrix metalloproteinases at restricted sites in colon anastomosis repair: an immunohistochemical and biochemical study},
  url          = {http://dx.doi.org/10.1016/j.surg.2005.12.013},
  volume       = {140},
  year         = {2006},
}