Experimental models

Observations on the behaviour of circulating leukocytes are difficult. However, techniques such as time-lapse and intravascular microscopy on rabbit ear, mesenteric tissue of mouse or rat, hamster cheek pouch or bat wing enabled us to monitor intravascular events and diapedesis. Radiolabeled blood cells ("'In or 92Tc) are useful tools for studying the kinetics and clearance of cells from the blood circulation and for monitoring differences in cell distribution and extravasation to the distinct tissue compartments.

Unfortunately these methods offer little insight into the molecular mechanism(s) underlying cellular adherence and diapedesis. Progress in identifying the mechanisms involved has been dependent on the development of in vitro systems that not only permit the adherence of cells to endothelial cells but also allow these cells to penetrate and traverse the endothelial monolayer, including the underlying basement membrane. One approach involves the interaction of cells with monolayers of endothelial cells grown on nitrocellulose or polycarbonate filters. Biological membranes, such as the mesenteric membrane or amnionic membrane, or layers of cultured smooth muscle cells also serve as excellent carriers for endothelial cells in this respect. The endothelial cells used for these in vitro studies are usually harvested from large vessels, as isolation and cultivation are fairly simple and do not require expensive equipment or advanced techniques. However, diapedesis of leukocytes in vivo is more prominent in capillaries, postcapillary venules and small venules than in macro-vessels and occurs during constant blood flow. Therefore, during the past few years, there has been enormous interest in the isolation and culture of microvascular endothelial cells from distinct vascular sites and in the development of new techniques to study adhesion and subsequent diapedesis of leukocytes under flow conditions.

See also: Adhesion molecules; Chemokines; Cytokines; Endothelium; Integrins; Lymphocyte trafficking; Recruitment; Selectins (CD62-E/L/P).

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