Human Siglec-10 can bind to vascular adhesion protein-1 and serves as its substrate

Elina Kivi, Kati Elima, Kristiina Aalto, Yvonne Nymalm, Kaisa Auvinen, Erkki Koivunen, Diana M. Otto, Paul R. Crocker, Tiina A. Salminen, Marko Salmi, Sirpa Jalkanen

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    53 Citations (Scopus)

    Abstract

    Leukocytes migrate from the blood into areas of inflammation by interacting with various adhesion molecules on endothelial cells. Vascular adhesion protein-1 (VAP-1) is a glycoprotein expressed on inflamed endothelium where it plays a dual role: it is both an enzyme that oxidizes primary amines and an adhesin that is involved in leukocyte trafficking to sites of inflammation. Although VAP-1 was identified more than 15 years ago, the counterreceptor(s) for VAP-1 on leukocytes has remained unknown. Here we have identified Siglec-10 as a leukocyte ligand for VAP-1 using phage display screenings. The binding between Siglec-10 and VAP-1 was verified by different adhesion assays, and this interaction was also consistent with molecular modeling. Moreover, the interaction between Siglec-10 and VAP-1 led to increased hydrogen peroxide production, indicating that Siglec-10 serves as a substrate for VAP-1. Thus, the Siglec-10-VAP-1 interaction seems to mediate lymphocyte adhesion to endothelium and has the potential to modify the inflammatory microenvironment via the enzymatic end products. (Blood. 2009; 114: 5385-5392)

    Original languageEnglish
    Pages (from-to)5385-5392
    Number of pages8
    JournalBlood
    Volume114
    Issue number26
    Early online date27 Oct 2009
    DOIs
    Publication statusPublished - 17 Dec 2009

    Keywords

    • Genetic algorithm
    • Oxidase activity
    • Amine oxidase
    • Lymph nodes
    • VAP-1
    • Endothelium
    • Recognition
    • Cloning
    • Transmigration
    • Molecule

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