Interactions between leukocytes and endothelial cells in vitro

The effector functions of leukocytes, such as secretion of antibodies and inflammatory mediators, endocytosis of soluble and particulate materials including pathogenic microorganisms, and remodeling and reabsorption of extracellular matrices, occur in extravascular tissues. To reach this extravascular compartment from the bloodstream, leukocytes must adhere to and traverse the endothelium that lines the vessel walls. Electron microscopic studies of leukocyte emigration in vivo (1–7) have revealed the basic sequence of events that occurs during this process. Within minutes after a local injury occurs, leukocytes adhere tightly to the endothelium of vessels, particularly postcapillary venules, in the affected area. The leukocytes then insert pseudopods between endothelial cells, and eventually the white cells traverse the width of the endothelial layer. Often, the leukocytes subsequently become trapped between the endothelium and its underlying basement membrane, but with time the white cells breach the periendothelial structures and move out into the surrounding connective tissue. Nearly all of the cells that initially migrate in response to mild injury are polymorphonuclear leukocytes (PMNs), however, cells that resemble eosinophils or monocytes have been observed crossing the endothelium in a manner similar to that of PMNs (1–5). Although the usual route of migration in inflamed tissues appears to be through intercellular junctions of the endothelium (2, 4, 5, 7), transcellular passage occurs in the myeloid sinuses of the bone marrow and in venules of the lymph node (reviewed in reference 8). In these cases, blood cells penetrate the body of an endothelial cell via a ‘migration pore’ that closes following passage of the leukocyte.