Leukocyte Adhesion to Endothelium in Vitro Under Shear Stress

Endothelial cells separate the blood from the environment of local tissues, but also mediate signals between these two compartments and facilitate directed leukocyte migration. Leukocyte transmigration through the blood vessel wall is part of the recirculation pathway of mononuclear leukocytes between the blood and the lymphatic system, and it is essential for leukocyte extravasation into sites of inflammation. Leukocyte adhesion to the endothelial cells of the blood vessel wall is the first step of leukocyte extravasation. In vitro cell-cell adhesion assays have contributed to the identification and functional analysis of cell adhesion molecules which are important for the interaction of leukocytes with endothelium. Different leukocyte subsets accumulate outside the vascular wall, dependent on the type of inflammatory insult. In vitro assays allow the study of the individual adhesion characteristics of distinct leukocyte subsets like polymorphonuclear granulocytes (PMN), eosinophilic granulocytes, T and B lymphocytes, or monocytes under defined conditions. Endothelial cell adhesion molecules relevant for leukocyte adhesion include members of the selectin family (E-selectin and P-selectin) as well as immunoglobulin superfamily molecules ICAM-1 and ICAM-2,VCAM-1, the JAM family, and members of the mucin-type cell surface molecules like CD34, GlyCAM-1, or MADCAM-1 (Butcher and Picker 1996, Johnston and Butcher 2002, Patel et al. 2002, Vestweber and Blanks 1999).