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.
Kivi
Elina
E
MediCity Research Laboratory, University of Turku, Turku, Finland.
Elima
Kati
K
Aalto
Kristiina
K
Nymalm
Yvonne
Y
Auvinen
Kaisa
K
Koivunen
Erkki
E
Otto
Diana M
DM
Crocker
Paul R
PR
Salminen
Tiina A
TA
Salmi
Marko
M
Jalkanen
Sirpa
S
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)