The Junctional Adhesion Molecule-C Promotes Neutrophil Transendothelial Migration in Vitro and in Vivo

The third member of the family of junctional adhesion molecules (JAMs), JAM-3, also called JAM-C, was recently shown to be a novel counter-receptor on platelets for the leukocyte β2-integrin Mac-1 (αMβ2, CD11b/CD18). Here, new functional aspects of the role of endothelial cell JAM-C were investigate...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 2004-12, Vol.279 (53), p.55602-55608
Main Authors: Chavakis, Triantafyllos, Keiper, Tanja, Matz-Westphal, Rachel, Hersemeyer, Karin, Sachs, Ulrich J., Nawroth, Peter P., Preissner, Klaus T., Santoso, Sentot
Format: Article
Language:English
Subjects:
Animals
Blotting, Western
Cell Adhesion
Cell Adhesion Molecules - chemistry
Cell Adhesion Molecules - physiology
Cell Movement
Cells, Cultured
Endothelial Cells - metabolism
Endothelium, Vascular - cytology
Flow Cytometry
Humans
Immunoblotting
Immunoglobulins - chemistry
Immunoglobulins - physiology
In Vitro Techniques
Inflammation
Junctional Adhesion Molecules
Membrane Proteins - chemistry
Membrane Proteins - metabolism
Membrane Proteins - physiology
Mice
Microscopy, Fluorescence
Neutrophils - cytology
Neutrophils - metabolism
Peritonitis - pathology
Phosphoproteins - metabolism
Protein Binding
Tetradecanoylphorbol Acetate - pharmacology
Zonula Occludens-1 Protein
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The third member of the family of junctional adhesion molecules (JAMs), JAM-3, also called JAM-C, was recently shown to be a novel counter-receptor on platelets for the leukocyte β2-integrin Mac-1 (αMβ2, CD11b/CD18). Here, new functional aspects of the role of endothelial cell JAM-C were investigated. Endothelial cells express JAM-C, which is predominantly localized within junctions at interendothelial contacts, since it codistributes with a tight junction component, zonula occludens-1. Whereas JAM-C does not participate in neutrophil adhesion to endothelial cells, it mediates neutrophil transmigration in a Mac-1-dependent manner. In particular, inhibition of JAM-C significantly reduced neutrophil transendothelial migration, and the combination of JAM-C and platelet/endothelial cell adhesion molecule-1 blockade almost completely abolished neutrophil transendothelial migration in vitro. In vivo, inhibition of JAM-C with soluble mouse JAM-C resulted in a 50% reduction of neutrophil emigration in the mouse model of acute thioglycollate-induced peritonitis. Thus, JAM-C participates in neutrophil transmigration and thereby provides a novel molecular target for antagonizing interactions between vascular cells that promote inflammatory vascular pathologies.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M404676200