Cloning of an Immunoglobulin Family Adhesion Molecule Selectively Expressed by Endothelial Cells

Abstract

To gain fundamental information regarding the molecular basis of endothelial cell adhesive interactions during vascular formation, we have cloned and characterized a unique cell adhesion molecule. This molecule, named endothelial cell-selective adhesion molecule (ESAM), is a new member of the immunoglobulin superfamily. The conceptual protein encoded by cDNA clones consists of V-type and C2-type immunoglobulin domains as well as a hydrophobic signal sequence, a single transmembrane region, and a cytoplasmic domain. Northern blot analysis showed ESAM to be selectively expressed in cultured human and murine vascular endothelial cells and revealed high level expression in lung and heart and low level expression in kidney and skin. In situ hybridization analysis indicated that ESAM is primarily expressed in the developing vasculature of the embryo in an endothelial cell-restricted pattern. Epitope-tagged ESAM was shown to co-localize with cadherins and catenins in cell-cell junctions. In aggregation assays employing ESAM-expressing Chinese hamster ovary cells, this novel molecule was shown to mediate cell-cell adhesion through homophilic interactions. The endothelial cell-selective expression of this immunoglobulin-like adhesion molecule coupled with its in vitro functional profile strongly suggests a role in cell-cell interactions that is critical for vascular development or function.

IgE-activated basophils regulate eosinophil tissue entry by modulating endothelial function

“…VCAM-1 was not required for basophil entry into the tissue, which reflects the lack of 4-integrins on mouse basophils (Voehringer et al, 2004). To assess the role of basophils in modulating endothelial VCAM-1, we analyzed VCAM-1 expression by flow cytometry on ear endothelial cells (CD45  CD34 + ESAM-1 + ) from sensitized ears 40 h after challenge (Baumhueter et al, 1994;Hirata et al, 2001). VCAM-1 + endothelial cells were present in these mice, and expression of endothelial VCAM-1 was reduced when basophils were deleted using Basoph8 × Rosa-DTA mice (Fig.…”

Targeted Disruption of Endothelial Cell-selective Adhesion Molecule Inhibits Angiogenic Processes in Vitro and in Vivo

“…A novel endothelial cell surface protein of the immunoglobulin superfamily has been cloned recently in this laboratory and named endothelial cell-selective adhesion molecule (ESAM) (12). Previous studies have determined that ESAM expression is restricted to endothelial cells in the embryonic and adult vasculature (12,13).…”

“…Previous studies have determined that ESAM expression is restricted to endothelial cells in the embryonic and adult vasculature (12,13). ESAM has been shown to me-diate homophilic and calcium-independent adhesion of expressing cells (12).…”

Positive and negative regulation of adenovirus infection by CAR-like soluble protein, CLSP

“…The results revealed that the closest relative to CLSP is CAR, followed by CLMP, 15 BT-IgSF 16 and ESAM. 17 Figure 8a shows a phylogenetic tree of the IgV domains of CAR and CLMP for the mouse, rat, human, bovine and chicken and three IgV domains of CLSP for the mouse and rat. The tree suggests that the segmental duplication including the first three exons of CAR occurred before the divergence of rodents and other mammals.…”

“…14 For example, CAR is structurally similar to CAR-like membrane protein (CLMP), 15 brain-and testis-specific Ig superfamily (BT-IgSF), 16 and endothelial cell-selective adhesion molecule (ESAM). 17 Another characteristic is that many of the Ig-superfamily genes produce soluble receptors that lack the transmembrane and cytoplasmic domains of full-length receptors. 18 Each of the soluble receptors is produced by proteolytic cleavage of the original membrane-bound receptor or de novo synthesis from alternatively spliced RNAs that are specific for the soluble receptor.…”