Vascular Endothelial Junction-associated Molecule, a Novel Member of the Immunoglobulin Superfamily, Is Localized to Intercellular Boundaries of Endothelial Cells*

Abstract

During the process of lymphocyte homing to secondary lymphoid organs, such as lymph nodes and tonsils, lymphocytes interact with and cross a specialized microvasculature, known as high endothelial venules. There is a great deal of information available about the first steps in the homing cascade, but molecular understanding of lymphocyte transmigration through the intercellular junctions of high endothelial venules is lacking. In analyzing expressed sequence tags from a cDNA library prepared from human tonsillar high endothelial cells, we have identified a cDNA encoding a novel member of the immunoglobulin superfamily. The protein, which we have termed VE-JAM (“vascular endothelial junction-associated molecule”), contains two extracellular immunoglobulin-like domains, a transmembrane domain, and a relatively short cytoplasmic tail. VE-JAM is prominently expressed on high endothelial venules but is also present on the endothelia of other vessels. Strikingly, it is highly localized to the intercellular boundaries of high endothelial cells. VE-JAM is most homologous to a recently identified molecule known as Junctional Adhesion Molecule, which is concentrated at the intercellular boundaries of both epithelial and endothelial cells. Because the Junctional Adhesion Molecule has been strongly implicated in the processes of neutrophil and monocyte transendothelial migration, an analogous function of VE-JAM during lymphocyte homing is plausible.

Footnotes

  • * This work was supported by the National Institutes of Health MERIT Award R37GM23547, Roche Bioscience, and the Northern California Arthritis Foundation.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) and .

  • To whom correspondence should be addressed. Tel.: 415-476-1579; Fax: 415-476-4845; E-mail: sdr@itsa.ucsf.edu.

  • Published, JBC Papers in Press, April 21, 2000, DOI 10.1074/jbc.M003189200

  • Abbreviations:
    HEV

    high endothelial venule(s)

    HEC

    high endothelial cell(s)

    EST

    expressed sequence tag

    IgSF

    immunoglobulin superfamily

    VE-JAM

    vascular endothelial junction-associated molecule

    PCR

    polymerase chain reaction

    bp

    base pairs

    PBL

    peripheral blood lymphocyte(s)

    CHO

    chinese hamster ovary cell

    PBS

    phosphate-buffered saline

    GST

    glutathione S-transferase

    JAM

    junctional adhesion molecule

    PECAM-1

    platelet endothelial cell adhesion molecule-1

    • Received April 13, 2000.
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