Ischemia/reperfusion-induced leukocyte-endothelial interactions in postcapillary venules

Abstract

The recruitment of leukocytes into postcapillary venules following reperfusion of ischemic tissues is a classical inflammatory response that is influenced by a balance of adhesive and hemodynamic forces. Initial periods of reperfusion are characterized by an elevation in low affinity adhesive interactions between leukocytes and endothelial cells, which permit the leukocytes to establish intimate contact with the vascular endothelial lining as they roll across it. This rolling behavior of leukocytes increases the probability that stronger adhesive interactions between leukocyte and endothelial cell will occur, allowing the leukocyte to firmly adhere to the endothelium and subsequently to emigrate across the venular wall into the interstitial compartment. Several factors appear to contribute to the leukocyte-endothelial cell adhesion that is elicited by ischemia/reperfusion, including: 1) the magnitude of adhesion molecule expression on leukocyte and/or endothelial cell surfaces, 2) reactive oxygen metabolites and lipid mediators released from stimulated leukocytes and endothelial cells and 3) hemodynamic dispersal forces that act to sweep leukocytes from the microvessel wall. Intravital microscopic techniques have allowed investigators to focus on inflammatory responses in postcapillary venules, which is the primary site of leukocyte adhesion and vascular protein leakage. This technology has also been employed to delineate the role of adhesive and hemodynamic factors in promoting leukocyte rolling, adhesion, and emigration in postcapillary venules exposed to ischemia/reperfusion.