Inhibition of rat gut reperfusion injury with an agent developed for the mouse. Evidence that amplification of injury by innate immunity is conserved between two animal species

Murine reperfusion injury follows binding of specific IgM natural antibodies to neo-antigens exposed in ischemic tissue. Peptides that mimic the site of antibody binding in the injury prevent IgM binding when administered intravenously before reperfusion. To determine whether this pathogenic sequence is restricted to mice, we have tested the ability of the peptide to prevent reperfusion injury in a dissimilar species, the rat. Sprague-Dawley rats were subjected to 40 min of mesenteric ischemia followed by 180 min of reperfusion. The peptide mimic was administered intravenously prior to reperfusion. Gut injury was quantified using a scoring system based on the hematoxylin-and-eosin section. (125)I-labeled albumin was used to assess local (gut) and remote (lung) injury. The macroscopic appearance of bowel from peptide-treated animals was less edematous and hemorrhagic. Microscopic analysis showed a significantly reduced injury score in peptide-treated animals. Permeability data indicated a significant reduction in local and remote injury in peptide-treated animals. The data demonstrate attenuation of rat gut microvillus injury, of gut edema, and of remote injury following mesenteric ischemia-reperfusion due to administration of an intravenous peptide mimic of a murine ischemia neo-antigen, indicating a second species uses a similar ischemia neo-antigen and corresponding natural antibody specificity to amplify reperfusion injury to the point of necrosis. This mechanism of inflammation is potentially applicable to higher species.