JAM-C regulates unidirectional monocyte transendothelial migration in inflammation.
Monocyte recruitment from the vasculature involves sequential engagement of multiple receptors, culminating in transendothelial migration and extravasation. Junctional adhesion molecule-C (JAM-C) is localized at endothelial intercellular junctions and plays a role in monocyte transmigration. Here, we show that blockade of JAM-B/-C interaction reduced monocyte numbers in the extravascular compartment through increased reverse transmigration rather than by reduced transmigration. This was confirmed in vivo, showing that an anti-JAM-C antibody reduced the number of monocytes in inflammatory tissue and increased the number of monocytes with a reverse-transmigratory phenotype in the peripheral blood. All together, our results suggest a novel mechanism of reducing accumulation of monocytes at inflammation sites by disruption of JAM-C-mediated monocyte retention.
Bradfield
Paul F
PF
Department of Pathology and Immunology, University Medical Centre, Geneva, Switzerland.
Scheiermann
Christoph
C
Nourshargh
Sussan
S
Ody
Christiane
C
Luscinskas
Francis W
FW
Rainger
G Ed
GE
Nash
Gerard B
GB
Miljkovic-Licina
Marijana
M
Aurrand-Lions
Michel
M
Imhof
Beat A
BA
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001792:Blood Platelets / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002465:Cell Movement; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D062726:Junctional Adhesion Molecules; D051379:Mice; D008822:Mice, Transgenic; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism*; D010641:Phenotype
D000906:Antibodies; D015815:Cell Adhesion Molecules; D062726:Junctional Adhesion Molecules