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 leukosequestration and injury, We now examine the intermediary role of selectins and complement in mediating lung and liver injury after hindlimb ischemia, Methods: Mice underwent a 2-hour bilateral tourniquet hindlimb ischemia followed by 3 hours of reperfusion. Results: Neutrophil depletion significantly decreased lung vascular permeability index (PI), measured by the extravasation of I-125-albumin, and liver injury as assessed by serum alanine aminotransferse levels. Lung PI and serum alanine aminotransferse levels were also reduced in mice treated with recombinant soluble P-selectin glycoprotein ligand-immunoglobulin fusion protein. Complement inhibition with soluble complement receptor type 1 decreased lung PI and serum alanine aminotransferse levels. C5-deficient mice exhibited 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 and complement dependent.