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.


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.
Scheiermann
Christoph
C
Barts and The London School of Medicine and Dentistry, Queen Mary University of London, William Harvey Research Institute, London, UK.
Colom
Bartomeu
B
Meda
Paolo
P
Patel
Nimesh S A
NS
Voisin
Mathieu-Benoit
MB
Marrelli
Alessandra
A
Woodfin
Abigail
A
Pitzalis
Costantino
C
Thiemermann
Christoph
C
Aurrand-Lions
Michel
M
Imhof
Beat A
BA
Nourshargh
Sussan
S
D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000502:physiology*; D002465:Cell Movement; D042783:Endothelial Cells / Q000378:metabolism; D007136:Immunoglobulins / Q000032:analysis / Q000502:physiology*; D007668:Kidney / Q000098:blood supply; D007962:Leukocytes / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000098:blood supply; D015427:Reperfusion Injury / Q000473:pathology*
D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C486723:Jam3 protein, mouse