The vascular endothelium, positioned at the interface between the components of the blood and the interstitial milieu, plays a strategic role in the control of vascular physiology and maintenance of body homeostasis. It directs transendothelial gradients of molecules, regulates vascular tone, controls thrombosis, and is a crucial regulator of vascular redox state (1–4). Additionally, one of the most intensely studied and best characterized functions of endothelial cells (ECs) is their participation in innate and adaptive immunity, key steps in response to infection and tissue injury (5).

In a complex and elegantly coordinated process, ECs orchestrate the focal adhesion of white blood cells (WBCs) to the vessel wall and their migration into damaged tissue. This normally takes place at the level of postcapillary venules, and is governed in large part by the interaction of complementary adhesion molecules on the EC and leukocyte surfaces (Table 117–1). The generation of vasoactive compounds (e.g., prosta-cyclin, nitric oxide [NO]) by ECs causes vascular smooth muscle cell (VSMC) relaxation and local vasodilatation, increasing the blood flow at the site of injury and facilitating local accumulation of leukocytes (6). Flowing WBCs that collide with activated endothelium may bind to ECs through low-affinity receptors – the endothelial selectins (P- and E-selectin) – that recognize carbohydrate-based ligands on the leukocyte surface (Figure 117.1). The combined effects of blood flow and leukocyte binding to selectins result in their rolling on the EC surface. Chemotactic agents produced by ECs promote further rolling and facilitate firm adhesion via the induction of integrins on the surface of leukocytes. These integrins bind to high-affinity cell adhesion molecules (CAMs), most notably vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 (7).