Human Siglec-10 can bind to vascular adhesion protein-1 and serves as its substrate.
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.
MediCity Research Laboratory, University of Turku, Turku, Finland.
Elina
E
Kivi
Kati
K
Elima
Kristiina
K
Aalto
Yvonne
Y
Nymalm
Kaisa
K
Auvinen
Erkki
E
Koivunen
Diana M
DM
Otto
Paul R
PR
Crocker
Tiina A
TA
Salminen
Marko
M
Salmi
Sirpa
S
Jalkanen
D006631:Amine Oxidase (Copper-Containing) / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D006224:Cricetinae; D003412:Cricetulus; D004727:Endothelium / Q000276:immunology / Q000378:metabolism; D006801:Humans; D037102:Lectins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D019151:Peptide Library; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins
D015815:Cell Adhesion Molecules; D037102:Lectins; D008024:Ligands; D019151:Peptide Library; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C426228:SIGLEC10 protein, human; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing)