Neutrophil mediated remote organ injury after lower torso ischemia and reperfusion is selectin and complement dependent

Background: Lower torso ischemia and reperfusion leads to remote organ leuk osequestration and injury, We now examine the intermediary role of selectin s and complement in mediating lung and liver injury after hindlimb ischemia , Methods: Mice underwent a 2-hour bilateral tourniquet hindlimb ischemia fol lowed by 3 hours of reperfusion. Results: Neutrophil depletion significantly decreased lung vascular permeab ility index (PI), measured by the extravasation of I-125-albumin, and liver injury as assessed by serum alanine aminotransferse levels. Lung PI and se rum alanine aminotransferse levels were also reduced in mice treated with r ecombinant soluble P-selectin glycoprotein ligand-immunoglobulin fusion pro tein. Complement inhibition with soluble complement receptor type 1 decreas ed lung PI and serum alanine aminotransferse levels. C5-deficient mice exhi bited a similar decrease in lung PI and liver injury. Lung and liver injury were restored in C5-deficient mice reconstituted with wild-type serum. Conclusion: Remote organ injury after lower torso reperfusion is selectin a nd complement dependent.