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 ⁶⁸Gallium-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.
2011-09-30
Eng.
Blood
MediCity Research Laboratory and Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.
Blood. 2011 Sep;118(13):3725-33
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