Format

Send to

Choose Destination
See comment in PubMed Commons below
Arterioscler Thromb Vasc Biol. 2013 Oct;33(10):2366-73. doi: 10.1161/ATVBAHA.113.301221. Epub 2013 Aug 15.

Recombinant lectin-like domain of thrombomodulin suppresses vascular inflammation by reducing leukocyte recruitment via interacting with Lewis Y on endothelial cells.

Author information

1
From the Department of Biochemistry and Molecular Biology (W.-L.L., C.-S.S., G.-Y.S., H.-L.W.); Institute of Basic Medical Sciences (W.-L.L.); Cardiovascular Research Center (W.-L.L., G.-Y.S., H.-L.W.); Center of Bioscience and Biotechnology (H.-L.W.); and Department of Medical Laboratory Science and Biotechnology (C.-F.C.), College of Medicine, National Cheng Kung University, Tainan City, Taiwan.

Erratum in

  • Arterioscler Thromb Vasc Biol. 2013 Nov;33(11):e135.

Abstract

OBJECTIVE:

The N-terminal lectin-like domain (domain 1 [D1]) of thrombomodulin (TM) is known to have an anti-inflammatory function. We previously showed that recombinant TM domain 1 (rTMD1) interacts with a carbohydrate molecule, Lewis Y (Le(y)), which is found to be expressed on adhesion molecules and involved in cell adhesion. Here, we tested the effect of rTMD1/Le(y) interaction on leukocyte recruitment in inflammation.

APPROACH AND RESULTS:

The expression of Le(y) on the surface of human umbilical vein endothelial cells was increased by tumor necrosis factor-α stimulation. Direct binding of rTMD1 to Le(y) on the cell surface was observed. rTMD1 inhibited Le(y)-mediated leukocyte adhesion on the Le(y)-immobilized flow chamber and activated endothelium under a shear flow. The following leukocyte transmigration to endothelium was also reduced by rTMD1 through binding Le(y). In vivo, treatment of rTMD1 reduced leukocyte recruitment to the inflammatory sites in carotid ligation injury and thioglycollate-induced peritonitis. rTMD1 administration in apolipoprotein E-deficient mice effectively suppressed atherosclerotic plaque formation and macrophage infiltration in atherosclerotic lesions. Increased Le(y) expression, as well as administered rTMD1, was observed in inflamed vessels.

CONCLUSIONS:

rTMD1 suppresses vascular inflammation by inhibiting leukocyte recruitment to endothelium through attenuating Le(y)-mediated adhesion and further protects against atherosclerosis progression. The present study provides a mechanism showing that rTMD1 can inhibit inflammation by binding to its carbohydrate ligand Le(y).

KEYWORDS:

Lewis Y antigen; atherosclerosis; inflammation; leukocytes; thrombomodulin

PMID:
23950139
DOI:
10.1161/ATVBAHA.113.301221
[Indexed for MEDLINE]
Free full text

Publication type, MeSH terms, Substances

Publication type

MeSH terms

Substances

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center