Siglec-9 is a novel leukocyte ligand for vascular adhesion protein-1 and can be used in PET imaging of inflammation and cancer

Kristiina Aalto, Anu Autio, Elina A. Kiss, Kati Elima, Yvonne Nymalm, Tibor Z. Veres, Fumiko Marttila-Ichihara, Heli Elovaara, Tiina Saanijoki, Paul R. Crocker, Mikael Maksimow, Eva Bligt, Tiina A. Salminen, Marko Salmi, Anne Roivainen, Sirpa Jalkanen

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    Abstract

    Leukocyte migration to sites of inflammation is regulated by several endothelial adhesion molecules. Vascular adhesion protein-1 (VAP-1) is unique among the homing-associated molecules as it is both an enzyme that oxidizes primary amines and an adhesin. Although granulocytes can bind to endothelium via a VAP-1-dependent manner, the counter-receptor(s) on this leukocyte population is(are) not known. Here we used a phage display approach and identified Siglec-9 as a candidate ligand on granulocytes. The binding between Siglec-9 and VAP-1 was confirmed by in vitro and ex vivo adhesion assays. The interaction sites between VAP-1 and Siglec-9 were identified by molecular modeling and confirmed by further binding assays with mutated proteins. Although the binding takes place in the enzymatic groove of VAP-1, it is only partially dependent on the enzymatic activity of VAP-1. In positron emission tomography, the (68)Gallium-labeled peptide of Siglec-9 specifically detected VAP-1 in vasculature at sites of inflammation and cancer. Thus, the peptide binding to the enzymatic groove of VAP-1 can be used for imaging conditions, such as inflammation and cancer. (Blood. 2011; 118(13):3725-3733)

    Original languageEnglish
    Pages (from-to)3725-3733
    Number of pages9
    JournalBlood
    Volume118
    Issue number13
    Early online date5 Aug 2011
    DOIs
    Publication statusPublished - 29 Sep 2011

    Keywords

    • Endothelial cell recognition
    • In vivo
    • Oxidase activity
    • Genetic algorithm
    • VAP-1
    • Binding
    • Recruitment
    • Receptor
    • Liver
    • Transmigration

    Cite this

    Aalto, K., Autio, A., Kiss, E. A., Elima, K., Nymalm, Y., Veres, T. Z., Marttila-Ichihara, F., Elovaara, H., Saanijoki, T., Crocker, P. R., Maksimow, M., Bligt, E., Salminen, T. A., Salmi, M., Roivainen, A., & Jalkanen, S. (2011). Siglec-9 is a novel leukocyte ligand for vascular adhesion protein-1 and can be used in PET imaging of inflammation and cancer. Blood, 118(13), 3725-3733. https://doi.org/10.1182/blood-2010-09-311076