Monocyte adhesion to rIL-4-stimulated human endothelial

The adhesion of leukocytes to endothelial cells (EC) is the first step required for the migration of leukocytes from blood to the tissue at sites of inflammation. These leukocyte-EC interactions are mediated by surface proteins (adhesion molecules) on both the leukocytes and the EC. Adhesion molecules that play a role in leukocyte-EC interactions are the β1- and β2-integrins on leukocytes and granule membrane protein-140 (GMP-140), endothelial leukocyte adhesion molecule-1 (ELAM-1), intercellular adhesion molecule-1 and 2 (ICAM-1 and ICAM-2) and vascular cell adhesion molecule-1 (VCAM-1) on EC. From earlier studies (1–11) with cultured human EC it is known that cytokines, like IL-la and TNF-a, can induce or up-regulate membrane expression of adhesion molecules on EC, thereby increasing leukocyte adhesion to the endothelium. Stimulation of EC with, for example, IL-la or TNF-a induces ELAM-1, an adhesion molecule involved in monocyte and granulocyte adhesion (2, 6). On the other hand IFN-7 increases the adhesiveness of EC for both monocytes and lymphocytes but not for neutrophils (12). Therefore the local production and release of various cytokines regulates the type and number of infiltrating leukocytes at the site of inflammation.