Human C1 esterase inhibitor attenuates murine mesenteric ischemia/reperfusion induced local organ injury

Background. Complement activation contributes to ischemia and reperfusion (IR)-initiated organ injury. C1 inhibitor (C1 Inh) inhibits the earliest steps of the classical and the mannose binding lectin pathways. Materials and methods. To determine whether C1 Inh prevented tissue injury, we performed intestinal IR experiments in BALB/c and C57BL/6 mice. Results. We found that C1 Inh limits mucosal injury in the two strains in a dose dependent manner. Tissue damage was associated with the accumulation of functional polymorphonuclear cells, which was reduced following C1 Inh treatment. Constitutive nitric oxide synthase activity correlated with the development of injury in the C57BL6 but not in the BALB/c mouse. Conclusions. These findings emphasize the importance of complement activation in ischemia/reperfusion and highlight the potential therapeutic use of C1 Inh in limiting or preventing damage caused by IR. (C) 2003 Elsevier Inc. All rights reserved.