Endothelial Leukocyte Adhesion Molecule 1: an Inducible Receptor for Neutrophils Related to Complement Regulatory Proteins and Lectins

Abstract

Focal adhesion of leukocytes to the blood vessel lining is a key step in inflammation and certain vascular disease processes. Endothelial leukocyte adhesion molecule-1 (ELAM-1), a cell surface glycoprotein expressed by cytokine-activated endothelium, mediates the adhesion of blood neutrophils. A full-length complementary DNA (cDNA) for ELAM-1 has now been isolated by transient expression in COS cells. Cells transfected with the ELAM-1 clone express a surface structure recognized by two ELAM-1 specific monoclonal antibodies (H4/18 and H18/7) and support the adhesion of isolated human neutrophils and the promyelocytic cell line HL-60. Expression of ELAM-1 transcripts in cultured human endothelial cells is induced by cytokines, reaching a maximum at 2 to 4 hours and decaying by 24 hours; cell surface expression of ELAM-1 protein parallels that of the mRNA. The primary sequence of ELAM-1 predicts an amino-terminal lectin-like domain, an EGF domain, and six tandem repetitive motifs (about 60 amino acids each) related to those found in complement regulatory proteins. A similar domain structure is also found in the MEL-14 lymphocyte cell surface homing receptor, and in granule-membrane protein 140, a membrane glycoprotein of platelet and endothelial secretory granules that can be rapidly mobilized (less than 5 minutes) to the cell surface by thrombin and other stimuli. Thus, ELAM-1 may be a member of a nascent gene family of cell surface molecules involved in the regulation of inflammatory and immunological events at the interface of vessel wall and blood.

A common missense single nucleotide polymorphism in the E-selectin gene is significantly associated with essential hypertension in the Han population but only weakly associated in the Uygur population

“…E-selectin was later found to mediate leukocyte adhesion to endothelial cells and their subsequent penetration of the vascular wall. 11 It is now clear that inflammatory factors affect BP by inducing the expression of adhesion molecules, mainly E-selectin, in endothelial tissue. Generally, E-selectin induces the adhesion and aggregation of leukocytes, which subsequently migrate into the vascular wall or extravascular space, thus injuring vascular endothelial cells, impairing endothelium-dependent vascular relaxation and finally leading to hypertension.…”

AICL: a new activation-induced antigen encoded by the human NK gene complex

“…4 A). A rapid, but transient increase in AICL mRNA was found between 1 and 8 h after stimulation with a maximal induction at 3 h. Although the induction of AICL mRNA is probably less pronounced, transcription kinetics of AICL are similar to CD69 Lopez-Cabrera et al 1993;Ziegler et al 1994) and other rapidly upregulated antigens such as tissue factor, CD62E, and CD97 (Scarpati and Sadler 1989;Bevilacqua et al 1989;Hamann et al 1995). The rapid mRNA turnover of these antigens is regulated by a fast degradation of the highly unstable mRNAs (Santis et al 1995).…”

Endothelial cell functions

“…In contrast to the vast majority of other adhesion molecules, the selectins mediate cell contact via binding to carbohydrate ligand structure and thus, they are lectins. L-selectin is found on most types of leukocytes (Finger et al, 1996), E-selectin is specific of endothelial cells (Bevilacqua et al, 1989) and P-selectin is found on endothelium and platelets (McEver et al, 1989).…”