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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 language | English |
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Pages (from-to) | 3725-3733 |
Number of pages | 9 |
Journal | Blood |
Volume | 118 |
Issue number | 13 |
Early online date | 5 Aug 2011 |
DOIs | |
Publication status | Published - 29 Sept 2011 |
Keywords
- Endothelial cell recognition
- In vivo
- Oxidase activity
- Genetic algorithm
- VAP-1
- Binding
- Recruitment
- Receptor
- Liver
- Transmigration
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Dive into the research topics of 'Siglec-9 is a novel leukocyte ligand for vascular adhesion protein-1 and can be used in PET imaging of inflammation and cancer'. Together they form a unique fingerprint.Projects
- 1 Finished
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Aref#d: 19149. Role of Siglecs in Disease (Senior Research Fellowship)
Crocker, P. (Investigator)
1/11/07 → 30/04/13
Project: Research