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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:1509.)
© 2009 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Junctional Adhesion Molecule-C Mediates Leukocyte Infiltration in Response to Ischemia Reperfusion Injury

Christoph Scheiermann; Bartomeu Colom; Paolo Meda; Nimesh S.A. Patel; Mathieu-Benoit Voisin; Alessandra Marrelli; Abigail Woodfin; Costantino Pitzalis; Christoph Thiemermann; Michel Aurrand-Lions; Beat A. Imhof; Sussan Nourshargh

From Barts and London School of Medicine and Dentistry (C.S., B.C., N.S.A.P., M.-B.V., A.M., A.W., C.P., C.T., S.N.), Queen Mary University of London, William Harvey Research Institute, London, UK; the Department of Cell Physiology and Metabolism (P.M.) and the Department of Pathology and Immunology (B.A.I.) University of Geneva, CMU, Switzerland; and INSERM (M.A.-L.), Centre de Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes, France. Current affiliation for C.S.: the Division of Hematology/Oncology, Mount Sinai School of Medicine, New York.

Correspondence to Sussan Nourshargh, WHRI, Barts and The London School of Medicine and Dentistry, QMUL, Charterhouse Square, London, EC1M 6BQ, UK. E-mail s.nourshargh{at}qmul.ac.uk

Objective— Junctional adhesion molecule-C (JAM-C) is an adhesion molecule that has multiple roles in inflammation and vascular biology, but many aspects of its functions under pathological conditions are unknown. Here we investigated the role of JAM-C in leukocyte migration in response to ischemia reperfusion (I/R) injury.

Methods and Results— Pretreatment of mice with soluble JAM-C (sJAM-C), used as a pharmacological blocker of JAM-C-mediated reactions, significantly suppressed leukocyte migration in models of kidney and cremaster muscle I/R injury (39 and 51% inhibition, respectively). Furthermore, in the cremaster muscle model (studied by intravital microscopy), both leukocyte adhesion and transmigration were suppressed in JAM-C-deficient mice (JAM-C^–/–) and enhanced in mice overexpressing JAM-C in their endothelial cells (ECs). Analysis of JAM-C subcellular expression by immunoelectron microscopy indicated that in I/R-injured tissues, EC JAM-C was redistributed from cytoplasmic vesicles and EC junctional sites to nonjunctional plasma membranes, a response that may account for the role of JAM-C in both leukocyte adhesion and transmigration under conditions of I/R injury.

Conclusions— The findings demonstrate a role for EC JAM-C in mediating leukocyte adhesion and transmigration in response to I/R injury and indicate the existence of a novel regulatory mechanism for redistribution and hence function of EC JAM-C in vivo.

Using a number of tools (eg, junctional adhesion molecule-C [JAM-C]^–/– mice), a role for JAM-C in leukocyte migration in response to ischemia/reperfusion (I/R) injury is shown. I/R injury also induced a redistribution of JAM-C in endothelial cells, which may provide a novel means of regulating the expression/function of JAM-C in vivo.

Key Words: JAM-C • ischemia reperfusion injury • leukocyte transmigration • inflammation • adhesion molecules