A BLOCKADE OF COMPLEMENT ACTIVATION PREVENTS RAPID INTESTINAL ISCHEMIA-REPERFUSION INJURY BY MODULATING MUCOSAL MAST-CELL DEGRANULATION IN RATS

We attempted to define the putative role of complement activation in a ssociation with mucosal mast cell (MMC) degranulation in the pathogene sis of rapid intestinal ischaemia-reperfusion (I/R) injury. We prepare d complement activity-depleted rats by the administration of the anti- complement agent K-76COOH and the serine-protease inhibitor FUT-175. A utoperfused segments of the jejunum were exposed to 60 min of ischaemi a, followed by reperfusion for various time periods, and the epithelia l permeability was assessed by the Cr-51-EDTA clearance rate. The numb er of MMC was immunohistochemically assessed. In control rats, the max imal increase in mucosal permeability was achieved by 30-45 min of rep erfusion. This increase was significantly attenuated by the administra tion of either K-76COONa alone or in combination with FUT-175. In cont rast, the administration of carboxypeptidase inhibitor (CPI), which pr events the inactivation of complement-derived anaphylatoxins such as C 5a, significantly enhanced the increase in I/R-induced mucosal permeab ility. These findings were confirmed morphologically by light microsco py and scanning electron microscopy. In addition, the I/R-induced muco sal injury was accompanied by a marked decrease in the number of MMC, and administration of K-76COOH significantly inhibited this change. Th ese results indicate that complement activation and the generation of complement-derived anaphylatoxins are key events in I/R-induced mucosa l injury. It is likely that intestinal I/R-induced mucosal injury may be partially mediated by MMC activation associated with the complement activation.