Human Siglec-10 can bind to vascular adhesion protein-1 and serves as its substrate

TY - JOUR

T1 - Human Siglec-10 can bind to vascular adhesion protein-1 and serves as its substrate

AU - Kivi, Elina

AU - Elima, Kati

AU - Aalto, Kristiina

AU - Nymalm, Yvonne

AU - Auvinen, Kaisa

AU - Koivunen, Erkki

AU - Otto, Diana M.

AU - Crocker, Paul R.

AU - Salminen, Tiina A.

AU - Salmi, Marko

AU - Jalkanen, Sirpa

PY - 2009/12/17

Y1 - 2009/12/17

N2 - 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. (Blood. 2009; 114: 5385-5392)

AB - 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. (Blood. 2009; 114: 5385-5392)

KW - Genetic algorithm

KW - Oxidase activity

KW - Amine oxidase

KW - Lymph nodes

KW - VAP-1

KW - Endothelium

KW - Recognition

KW - Cloning

KW - Transmigration

KW - Molecule

U2 - 10.1182/blood-2009-04-219253

DO - 10.1182/blood-2009-04-219253

M3 - Article

C2 - 19861682

SN - 0006-4971

VL - 114

SP - 5385

EP - 5392

JO - Blood

JF - Blood

IS - 26

ER -