Role of plasminogen activators in peritoneal adhesion formation.
Intra-abdominal adhesion formation is a major complication of serosal repair following surgery, ischaemia or infection, leading to conditions such as intestinal obstruction and infertility. It has been proposed that the persistence of fibrin, due to impaired plasminogen activator activity, results in the formation of adhesions between damaged serosal surfaces. This study aimed to assess the role of fibrinolysis in adhesion formation using mice deficient in either of the plasminogen activator proteases, tissue-type plasminogen activator (tPA) or urokinase-type plasminogen activator (uPA). We hypothesize that, following serosal injury, mice with decreased peritoneal fibrinolytic activity will be more susceptible to adhesion formation. Adhesion formation was induced in tPA- and uPA-deficient and wild-type mice following either surgical trauma to the serosa with haemorrhage and acute or chronic intraperitoneal inflammation. Adhesion formation was assessed from 1 to 4 weeks post-injury. Mice deficient in tPA were more susceptible to adhesion formation following both a surgical insult and a chronic inflammatory episode compared with uPA-deficient and wild-type mice. In addition, the time of maximal adhesion formation varied depending on the nature of the initial insult. It is proposed that the persistence of fibrin due to decreased tPA activity following surgery or chronic inflammation plays a major role in peritoneal adhesion formation.
Sulaiman
H
H
Department of Medicine, University College London, Rayne Institute, 5 University Street, London WC1E 6JJ, U.K.
Dawson
L
L
Laurent
G J
GJ
Bellingan
G J
GJ
Herrick
S E
SE
D000818:Animals; D005337:Fibrin / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D010532:Peritoneal Diseases / Q000201:enzymology* / Q000209:etiology*; D010960:Plasminogen Activators / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011183:Postoperative Complications / Q000201:enzymology / Q000209:etiology; D000267:Tissue Adhesions / Q000201:enzymology / Q000209:etiology
D005337:Fibrin; D010960:Plasminogen Activators