The junctional adhesion molecule JAM-C regulates polarized transendothelial migration of neutrophils in vivo
View/ Open
Published Version
Embargoed until: 5555-01-01
Embargoed until: 5555-01-01
Volume
12
Pagination
761 - U145
DOI
10.1038/ni.2062
Journal
NAT IMMUNOL
Issue
ISSN
1529-2908
Metadata
Show full item recordAbstract
The migration of neutrophils into inflamed tissues is a fundamental component of innate immunity. A decisive step in this process is the polarized migration of blood neutrophils through endothelial cells (ECs) lining the venular lumen (transendothelial migration (TEM)) in a luminal-to-abluminal direction. By real-time confocal imaging, we found that neutrophils had disrupted polarized TEM ('hesitant' and 'reverse') in vivo. We noted these events in inflammation after ischemia-reperfusion injury, characterized by lower expression of junctional adhesion molecule C (JAM-C) at EC junctions, and they were enhanced by blockade or genetic deletion of JAM-C in ECs. Our results identify JAM-C as a key regulator of polarized neutrophil TEM in vivo and suggest that reverse TEM of neutrophils can contribute to the dissemination of systemic inflammation.