Junctional adhesion molecule-C mediates leukocyte infiltration in response to ischemia reperfusion injury

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 [...] SCHEIERMANN, Christoph, et al. Junctional adhesion molecule-C mediates leukocyte infiltration in response to ischemia reperfusion injury. Arteriosclerosis, Thrombosis, and Vascular Biology, 2009, vol. 29, no. 10, p. 1509-15 DOI : 10.1161/ATVBAHA.109.187559