Role of complement activation and mast cell degranulation in the pathogenesis of rapid intestinal ischemia/reperfusion injury in rats.
The aim of this study is to define the putative role of complement activation and mucosal mast cell (MMC) degranulation in the pathogenesis of rapid ischemia-reperfusion (I/R) injury. We prepared complement activity-depleted rats by the administration of the anti-complementary agent K-76COONa. To assess the role of MMC degranulation, we used the MMC stabilizer MAR-99 and genetically mast cell-deficient Ws/Ws rats. Autoperfused segments of the jejunum were exposed to 60 min of ischemia, followed by 60 min reperfusion. The epithelial permeability was assessed by (51)Cr-EDTA clearance rate, and the number of MMC was immunohistochemically assessed. I/R treatment induced a marked increase in mucosal permeability and MMC degranulation. The treatment with K-76COONa and MAR-99 significantly attenuated these changes. Furthermore, in Ws/Ws rats the increase in mucosal permeability and MMC degranulation was significantly attenuated. These findings indicate the role of complement activation and MMC activation in the pathogenesis of rapid intestinal I/R injury. A regulation of the complement activation and MMC degranulation may be one of the clinical strategies for prevention of I/R-induced mucosal injury.
Andoh
A
A
Department of Internal Medicine, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Japan. andoh@belle.shiga-med.ac.jp
Fujiyama
Y
Y
Araki
Y
Y
Kimura
T
T
Tsujikawa
T
T
Bamba
T
T
D000818:Animals; D015550:Cell Degranulation; D002614:Chelating Agents / Q000493:pharmacokinetics; D003167:Complement Activation; D004492:Edetic Acid / Q000493:pharmacokinetics; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D007511:Ischemia / Q000473:pathology*; D007583:Jejunum / Q000098:blood supply* / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000502:physiology*; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000276:immunology* / Q000503:physiopathology*
D002614:Chelating Agents; D004492:Edetic Acid