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

K Aalto, A Autio, EA Kiss, K Elima, Y Nymalm, TZ Veres, F Marttila-Ichihara, H Elovaara, T Saanijoki, PR Crocker, M Maksimow, E Bligt, Tiina Salminen, M Salmi, A Roivainen, S Jalkanen

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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 languageUndefined/Unknown
Pages (from-to)3725–3733
Number of pages9
Issue number13
Publication statusPublished - 2011
MoE publication typeA1 Journal article-refereed

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