JAM-C regulates unidirectional monocyte transendothelial migration in inflammation

PF Bradfield, C Scheiermann… - Blood, The Journal …, 2007 - ashpublications.org
PF Bradfield, C Scheiermann, S Nourshargh, C Ody, FW Luscinskas, GE Rainger, GB Nash
Blood, The Journal of the American Society of Hematology, 2007ashpublications.org
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 …
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.
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