on July 2, 2009
Published online before print July 2, 2009, doi: 10.1161/ATVBAHA.109.187559
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Submitted on March 5, 2009
Accepted on June 16, 2009
Junctional Adhesion Molecule-C Mediates Leukocyte Infiltration in Response to Ischemia Reperfusion Injury
Christoph Scheiermann ;
From the Barts and The 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.
* To whom correspondence should be addressed. 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.
Key words: JAM-C • ischemia reperfusion injury • leukocyte transmigration • inflammation • adhesion molecules