Soluble Forms of Vascular Adhesion Molecules, E‐Selectin, ICAM‐1, and VCAM‐1: Pathological Significance

The emigration of circulating leukocytes into tissues is a characteristic of the inflammatory response. The extravasation of leukocytes and some tumor cells is controlled by the expression of cell sudice adhesion molecules on both the circulating cells and on the vascular endothelium.' We have produced monoclonal antibodies that bind to cytokine-activated human umbilical vein endothelial cells, and which can block the adhesion of leukocytes to the endothelium.2 These antibodies have been used to expression clone the adhesion molecules ICAM-1, VCAM-1 and E-Selectin (ELAM-1) (see TABLE 1). Functional studies using blocking monoclonal antibodies and mammalian cells stably transkcted with these adhesins have revealed their binding specificities. ICAM-1 will bind cells expressing the 62 integrins, or CD43, including lymphocytes, granulocytes, and m~nocy tes .~~ . " VCAM-1 will bind cells expressing the B1 integrin VLA4 (bla4), including lymphocytes, eosinophils, basophils, and m0nocytes.~-12 E-Selectin will bind granulocytes, monocytes and a subset of memory T cells (CLA+).l3-15 The identity of the physiological hgand(s) for E-Selectin on these cells is unclear; however, hcosylation and sialylation are thought to be important for binding. 16117 We have used monoclonal antibodies to investigte the expression ofadhesion molecules on endothelium and other tissues, in a range of inflammatory diseases. Reports