Complement inhibitor, complement receptor 1-related gene/protein y-Ig attenuates intestinal mesenteric ischemia/reperfusion damage after the onset ofinjury in mice

Complement receptor I-related gene/protein y (Crry) is a murine membrane pr otein that regulates the activity of both classical and alternative complem ent pathways. We used a recombinant soluble form of Crry fused to the hinge , CH2, and CH3 domains of mouse IgG1 (Crry-Ig) to determine whether inhibit ion of complement activation prevents and/or reverses mesenteric ischemia/ reperfusion-induced injury in mice. Mice were subjected to 30 min of ischem ia, followed by 2 h of reperfusion. Crry-Ig was administered either 5 min b efore or 30 min after initiation of the reperfusion phase. Pretreatment wit h Crry-Ig reduced local intestinal mucosal injury and decreased generation of leukotriene B-4 (LTB4). When given 30 min after the beginning of the rep erfusion phase, Crry-Ig resulted in a decrease in ischemia/reperfusion-indu ced intestinal mucosal injury comparable to that occurring when it was give n 5 min before initiation of the reperfusion phase. The beneficial effect o f Crry-Ig administered 30 min after the initiation of reperfusion coincided with a decrease in PGE(2) generation despite the fact that it did not prev ent local infiltration of neutrophils and did not have a significant effect on LTB4 production. These data suggest that complement inhibition protects animals from reperfusion-induced intestinal damage even if administered as late as 30 min into reperfusion and that the mechanism of protection is in dependent of neutrophil infiltration or LTB4 inhibition.