Human Brain Microvessel Endothelial Cell and Leukocyte Interactions

Abstract

The recruitment of leukocytes from the blood into secondary lymphoid and peripheral organs is a key process in both leukocyte homeostasis and the initiation and maintenance of immune responses (1). Within the past decade, several important advances have been made in identifying factors involved both in normal leukocyte homing and recruitment to sites of inflammation. These studies have identified adhesion molecules as instrumental in tethering leukocytes to endothelial surfaces and potentiating subsequent adhesion and migration. In addition, soluble chemoattractant cytokines (known as chemokines) have been identified that can direct the site and often the composition of the inflammatory infiltrate, as well as proteinases, which dismantle the barrier that leukocytes are crossing (2). In several of these studies, in vivo models have been used to block the activity of specific molecules in order to determine the global outcome and the involvement of these molecules in secondary lymphoid organ trafficking or disease pathogenesis. Such models, however, become of limited use when trying to focus on relative contributions to specific events such as direct cell-cell interactions occurring at the onset of inflammatory cell extravasation. Because of the complicated nature and multitude of cells and factors present in in vivo systems, in vitro models have become a powerful and more simplistic way of analyzing events by allowing for better control of the environment. For this purpose, in vitro models employing endothelial monolayers have been instrumental in trying to characterize factors which influence vascular permeability and the sequence of events during leukocyte-endothelial adhesion and transmigration.