title: A blockade of complement activation prevents rapid intestinal ischaemia-reperfusion injury by modulating mucosal mast cell degranulation in rats.
abstract: We attempted to define the putative role of complement activation in association with mucosal mast cell (MMC) degranulation in the pathogenesis of rapid intestinal ischaemia-reperfusion (I/R) injury. We prepared complement activity-depleted rats by the administration of the anti-complement agent K-76COOH and the serine-protease inhibitor FUT-175. Autoperfused segments of the jejunum were exposed to 60 min of ischaemia, followed by reperfusion for various time periods, and the epithelial permeability was assessed by the 51Cr-EDTA clearance rate. The number of MMC was immunohistochemically assessed. In control rats, the maximal increase in mucosal permeability was achieved by 30-45 min of reperfusion. This increase was significantly attenuated by the administration of either K-76COONa alone or in combination with FUT-175. In contrast, the administration of carboxypeptidase inhibitor (CPI), which prevents the inactivation of complement-derived anaphylatoxins such as C5a, significantly enhanced the increase in I/R-induced mucosal permeability. These findings were confirmed morphologically by light microscopy and scanning electron microscopy. In addition, the I/R-induced mucosal injury was accompanied by a marked decrease in the number of MMC, and administration of K-76COOH significantly inhibited this change. These results indicate that complement activation and the generation of complement-derived anaphylatoxins are key events in I/R-induced mucosal injury. It is likely that intestinal I/R-induced mucosal injury may be partially mediated by MMC activation associated with the complement activation.
authors.affiliation: Department of Internal Medicine, Shiga University of Medical Science, Seta-Tukinowa, Otsu, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kimura
authors.forename: A
authors.initials: A
authors.lastname: Andoh
authors.forename: Y
authors.initials: Y
authors.lastname: Fujiyama
authors.forename: T
authors.initials: T
authors.lastname: Saotome
authors.forename: T
authors.initials: T
authors.lastname: Bamba
mesh_terms: D000706:Anaphylatoxins / Q000494:pharmacology; D000818:Animals; D001550:Benzamidines; D015550:Cell Degranulation / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D002614:Chelating Agents / Q000493:pharmacokinetics; D002860:Chromium Radioisotopes; D003167:Complement Activation / Q000187:drug effects* / Q000502:physiology*; D003169:Complement Inactivator Proteins / Q000627:therapeutic use*; D004492:Edetic Acid / Q000493:pharmacokinetics; D006146:Guanidines / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000098:blood supply / Q000166:cytology* / Q000378:metabolism; D007511:Ischemia / Q000150:complications; D007583:Jejunum / Q000098:blood supply* / Q000166:cytology / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D012717:Sesquiterpenes / Q000627:therapeutic use*
chemical_list: D000706:Anaphylatoxins; D001550:Benzamidines; D002614:Chelating Agents; D002860:Chromium Radioisotopes; D003169:Complement Inactivator Proteins; D006146:Guanidines; D015842:Serine Proteinase Inhibitors; D012717:Sesquiterpenes; C038797:K 76 carboxylic acid; D004492:Edetic Acid; C032855:nafamostat