FIGURE 2

Lymphocyte adhesion to endothelial cells occurs in a series of stages. Free flowing lymphocyte subpopulations in the bloodstream (A + B) express different profiles of adhesion and chemokine receptors. Cells expressing appropriate counter receptors are captured by tethering or rolling receptors expressed on endothelial cells (1). Chemokine proteins localized on the glycocalyx of the endothelial cell are detected by specific, G-protein-linked receptors expressed on the leucocyte (2). This results in a conformational change in lymphocyte integrins, which permits firm adhesion of the lymphocyte to endothelial-expressed immunoglobulin adhesion molecules (3). Chemokine recognition also results in cytoskeletal reorganization within the adherent lymphocyte, which facilitates migration across the endothelial monolayer and into tissue (4). Once within the tissue the leucocyte follows a chemotactic gradient of chemokine signal towards the site of inflammation. Other cells in the microenvironment can affect the molecules expressed by the endothelium either by altering the differentiation in a tissue-specific manner (e.g. hepatocyte-derived growth factors drive the differentiation of sinusoidal endothelium), by secreting activationg factors, such as cytokines, that activate endothelium or by secreting chemokines that are then transported through the endothelium and presented within the glycocalyx.