Renal Expression of ICAM-1 and E-Selectin in Ischemia Reperfusion Injury and Sepsis † 1641

Abstract

Leukocyte adhesion and migration into injured tissue frequently contribute to the injury process in models of ischemia reperfusion injury and sepsis. Furthermore, adhesion molecule upregulation is crucial for the development of the inflammatory response and neutrophil activation. The current studies performed in models of acute renal injury in vivo evaluate the expression of two key leukocyte adhesion molecules, E-selectin, which is expressed exclusively by endothelial cells, and ICAM-1, which is distributed more ubiquitously in the kidney. A model of sepsis was produced in male C57/BL6 mice by administration of lipopolysaccharide (LPS) 2 mg/kg ip., previously demonstrated to induce adhesion molecules in lung tissue. LPS induced ICAM-1 and E-selectin mRNA in kidneys harvested 2h after dosing, and persisted at the 4h time point. Ischemia reperfusion injuriy (IRI) was produced by subjecting mice to 45 min of bilateral renal ischemia followed by reperfusion for up to 4 h. Induction of ICAM-1 was not seen by 2h of reperfusion, but was clearly evident by 3h and persisted at 4h. No upregulation of ICAM-1 mRNA was detected following ischemia without reperfusion, or in sham operated control mice. E-selectin mRNA was not induced by ischemia alone or ischemia with reflow up to 4h. In summary, 1) ICAM-1 message is induced by both LPS and IRI in renal tissue. 2) Post-ischemic reperfusion is required for the increase in ICAM-1 RNA. 3) mRNA for E-selectin is induced by LPS treatment, but is not increased by 4h of post-ischemic reperfusion. Our findings suggest that ICAM-1 mRNA upregulation may contribute to the development of inflammation in renal tissue exposed to IR or endotoxin, while E-selectin expression may contribute to inflammation in renal tissue exposed to endotoxin, but is not detectable following IRI.