Antibodies to ICAM-1 and PECAM-1 ameliorate pulmonary injury after intestinal ischemia-reperfusion in the rat

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Intestinal ischemia-reperfusion (I/R) gives rise to acute lung injury characterized by neutrophil sequestration and microvascular injury. Important mediators of I/R-associated injury include neutrophils and platelet-activating factor (PAF). During conditions of inflammation neutrophils and endothelial cells show an increased expression of adhesion molecules. ICAM-1 on endothelial cells is needed for high affinity bonds between neutrophils and endothelial cells, necessary for the further transmigration of neutrophils, where PECAM-1 is involved.

In the present study, a significant increase in albumin leakage over the pulmonary capillaries, as well as increased pulmonary MPO (myeloperoxidase)-content was found in rats subjected to 30 min intestinal ischemia (by clamping the superior mesenteric artery) followed by 12 h reperfusion. Treatment with anti-ICAM-1 or anti-PECAM-1 monoclonal antibodies significantly reduced the otherwise occuring increase in both albumin leakage and pulmonary MPO-content in pancreatitis animals. There was also an increase in serum IL-1β levels after intestinal I/R, which could be prevented by use of antibodies to ICAM-1 and PECAM-1.

In conclusion we found that the acute lung injury seen after intestinal I/R in the rat to a large extent could be prevented by blocking the adhesion/transmigration process of pulmonary leukocytes.