JAM-C regulates unidirectional monocyte transendothelial migration in inflammation

• Published in: Blood Vol. 110; no. 7; pp. 2545 - 2555
• Main Authors: Bradfield, Paul F., Scheiermann, Christoph, Nourshargh, Sussan, Ody, Christiane, Luscinskas, Francis W., Rainger, G. Ed, Nash, Gerard B., Miljkovic-Licina, Marijana, Aurrand-Lions, Michel, Imhof, Beat A.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.10.2007; The Americain Society of Hematology; American Society of Hematology
• Series: Immunobiology
• Subjects: Animals; Antibodies - immunology; Biological and medical sciences; Blood Platelets - metabolism; Cell Adhesion; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - immunology; Cell Adhesion Molecules - metabolism; Cell Movement; Cells, Cultured; Endothelial Cells - metabolism; Fundamental and applied biological sciences. Psychology; Humans; Immunobiology; Inflammation; Inflammation - metabolism; Inflammation - pathology; Junctional Adhesion Molecules; Mice; Mice, Transgenic; Molecular and cellular biology; Monocytes - cytology; Monocytes - metabolism; Phenotype; Monocyte; Leukocyte; Rodentia; Cell adhesion molecule; Inflammation; Endothelium; In vivo; Cell motility; Junctional adhesion molecule C; Vertebrata; Mammalia; Mouse; Animal; Cell migration
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2007-03-078733

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.