title: Action of matrix metalloproteinases at restricted sites in colon anastomosis repair: an immunohistochemical and biochemical study.
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.
authors.affiliation: Department of Surgery K, Bispebjerg Hospital, Copenhagen University Hospital, Denmark. maa02@bbh.hosp.dk
authors.forename: Magnus S
authors.initials: MS
authors.lastname: Agren
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Andersen
authors.forename: Ursula
authors.initials: U
authors.lastname: Mirastschijski
authors.forename: Ingvar
authors.initials: I
authors.lastname: Syk
authors.forename: Christine Bruun
authors.initials: CB
authors.lastname: Schiødt
authors.forename: Vikas
authors.initials: V
authors.lastname: Surve
authors.forename: Jan
authors.initials: J
authors.lastname: Lindebjerg
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Delaissé
mesh_terms: D000714:Anastomosis, Surgical / Q000009:adverse effects*; D000818:Animals; D003094:Collagen / Q000378:metabolism; D003106:Colon / Q000201:enzymology* / Q000473:pathology / Q000601:surgery*; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D013529:Surgical Wound Dehiscence / Q000201:enzymology / Q000209:etiology / Q000473:pathology; D013537:Sutures / Q000009:adverse effects
chemical_list: D003094:Collagen; D020782:Matrix Metalloproteinases; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9; D006909:Hydroxyproline