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

Surgery. 2006 Jul;140(1):72-82. doi: 10.1016/j.surg.2005.12.013.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anastomosis, Surgical / adverse effects*
  • Animals
  • Collagen / metabolism
  • Colon / enzymology*
  • Colon / pathology
  • Colon / surgery*
  • Humans
  • Hydroxyproline / metabolism
  • Immunohistochemistry
  • Male
  • Matrix Metalloproteinase 8 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinases / metabolism*
  • Models, Animal
  • Rats
  • Rats, Sprague-Dawley
  • Surgical Wound Dehiscence / enzymology
  • Surgical Wound Dehiscence / etiology
  • Surgical Wound Dehiscence / pathology
  • Sutures / adverse effects


  • Collagen
  • Matrix Metalloproteinases
  • Matrix Metalloproteinase 8
  • Matrix Metalloproteinase 9
  • Hydroxyproline