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

Colom, Bartomeu
Patel, Nimesh S A.
Voisin, Mathieu-Benoit
Marrelli, Alessandra
Woodfin, Abigail
Pitzalis, Costantino
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Published in Arteriosclerosis, thrombosis, and vascular biology. 2009, vol. 29, no. 10, p. 1509-15
Abstract 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.
Keywords AnimalsCell AdhesionCell Adhesion Molecules/analysis/physiologyCell MovementEndothelial Cells/metabolismImmunoglobulins/analysis/physiologyKidney/blood supplyLeukocytes/physiologyMiceMice, Inbred C57BLMice, TransgenicMuscle, Skeletal/blood supplyReperfusion Injury/pathology
PMID: 19574560
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Other version: http://atvb.ahajournals.org/cgi/content/full/29/10/1509
Research groups Couplage cellulaire et connexines (136)
L'influence du rôle du cycle circadien sur l'immunité (995)
Molécules d'adhésion et processus de migration cellulaire (167)
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SCHEIERMANN, Christoph et al. Junctional adhesion molecule-C mediates leukocyte infiltration in response to ischemia reperfusion injury. In: Arteriosclerosis, thrombosis, and vascular biology, 2009, vol. 29, n° 10, p. 1509-15. doi: 10.1161/ATVBAHA.109.187559 https://archive-ouverte.unige.ch/unige:5404

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Deposited on : 2010-03-12

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