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

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.

• Authors: 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
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 29 Issue 10 Pg. 1509-15 (Oct 2009) ISSN: 1524-4636 [Electronic] United States
• PMID: 19574560 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cell Adhesion Molecules
• Immunoglobulins
• Jam3 protein, mouse

Topics

• Animals
• Cell Adhesion
• Cell Adhesion Molecules (analysis, physiology)
• Cell Movement
• Endothelial Cells (metabolism)
• Immunoglobulins (analysis, physiology)
• Kidney (blood supply)
• Leukocytes (physiology)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Muscle, Skeletal (blood supply)
• Reperfusion Injury (pathology)