24 - Reactive Oxygen Species Increase Neutrophil Adherence to Endothelial Cells and Activate Tyrosine Phosphorylation of Cytoskeleton Proteins

Abstract

This chapter focuses on the involvement of adhesion molecules in the increased adherence of neutrophils to reactive oxygen species (ROS)-stimulated endothelial cells, on the oxygen species responsible for this adhesion, and on the intracellular-signaling pathway leading to cytoskeleton modification by ROS. Oxidative stress, defined as an increase in the production of ROS, such as superoxide anion (O2·-), hydrogen peroxide (H202), and hydroxyl radical (HO·), has been related to reperfusion injury in the heart and other organs. Several laboratories have shown that reperfusion of ischemic tissues leads to a marked local increase in the number of polymorphonuclear neutrophils (PMN) adhering to endothelial cells. The adherence of PMN to endothelial cells is related to many factors, especially adhesion molecules; the latter include intercellular adhesion molecule (ICAM-1), E-, and P-selectins on the endothelium, and L-selectin, β2 integrins, and carbohydrates such as sialyl-Lewis x on PMN. Endothelial cells also express platelet-activating factor (PAF), which binds to specific receptors on PMN. A large part of one's knowledge on the interaction of the endothelium with PMN is derived from in vitro studies using cultured endothelial cells isolated from human umbilical cord vein (HUVEC) and isolated PMN. Although these models are not strictly identical to in vivo conditions, they have shown that after exposure to histamine or thrombin, endothelial cells express P-selectin (GMP-140) and PAF within minutes.