The role of JAM‐C in leukocyte migration as induced by ischaemia/reperfusion injury in the mouse cremaster muscle

Numerous studies have implicated junctional adhesion molecule (JAM)‐C in leukocyte transendothelial cell migration in vitro but there remains little in vivo evidence for this. In this context, we have previously demonstrated a role for JAM‐C in migration of neutrophils in response to IL‐1 and LPS in the mouse cremaster muscle and lungs, respectively (Aurrand‐Lions et al., JI, 2005). To extend these findings, the aim of this study was to address the role of JAM‐C in leukocyte migration in response to ischaemia/reperfusion (I/R) injury. For this purpose, I/R (30 min ischaemia followed by 2 hrs reperfusion) was induced in the cremaster muscle of wild type (WT) mice and mice over‐expressing endothelial JAM‐C (Tg) and leukocyte responses of adhesion and transmigration were quantified by intravital microscopy. In WT mice, I/R led to a marked increase in the number of adherent and transmigrated leukocytes as compared to levels detected in sham operated animals and maximal adhesion and transmigration responses were observed at around 40 min and 80 min post start of the reperfusion period, respectively. In Tg mice, a marked increase in both leukocyte adhesion and transmigration was noted at every time‐point quantified, as compared to littermate controls (e.g. at 80 min time point 83% increase in transmigration was noted in Tg mice). These results provide direct in vivo evidence that endothelial cell JAM‐C can support leukocyte migration in response to I/R injury. Funded by the BHF U.K.