P-selectin mediates intestinal ischemic injury by enhancing complement deposition

Background. Ischemia and reperfusion injury of rodent intestine is complement mediated. P-seletin antagonism reduces local injury, yet neutrophil depletion does not. This study tests the thesis that the protective mechanism of P-selectin antagonists involves complement inhibition. Methods. We subjected rats (n=86) to 50 minutes of complete mesenteric ischemia and 4 hours of reperfusion. Treatment with a monoclonal antibody (PB1.3) against P-selectin reduced intestinal injury as judged by 125 I-albumin permeability index (7.33±0.40) compared with saline solution treatment (11.4±0.49) (p Results. However, intestinal neutrophil sequestration assessed by myeloperoxidase assay was unchanged. Immunohistochemistry revealed that mucosal C5b-9 was deposited in animals treated with saline solution and was absent in the sham group. PB1.3 treatment reduced C5b-9 deposition in the intestinal mucosa compared with that in animals treated with saline solution (p 125 I-albumin permeability and pulmonary myeloperoxidase assay were not significantly reduced by PB1.3. Treatment with a soluble form of P-selectin ligand, sialyl Lewis x (sLe x ), reduced intestinal myeloperoxidase (0.065±0.006) compared with saline solution treatment (0.136±0.02) (p −3 ) by sLe x compared with saline solution treatment (6.11±0.41×10 −3 ) (p Conclusions. Antagonizing the lectin domain of P-selectin and thereby neutrophil adhesion was without local benefit in this model. In contrast, PB1.3 exerted a novel antagonism of P-selectin and reduced complement deposition. (Surgery 1996;119:652–6.)