Effect of soluble JAM‐C on leukocyte transmigration in models of ischemia/reperfusion injury

Abstract

Numerous in vitro studies have implicated the adhesion molecule JAM‐C in leukocyte transendothelial cell migration but the role of JAM‐C in leukocyte migration in vivo requires further investigations. Here we used soluble JAM‐C (sJAM‐C) as a blocker of JAM‐C‐mediated reactions to investigate the role of this molecule in leukocyte transmigration in vivo as induced by ischemia/reperfusion (I/R). The study employed a murine model of kidney I/R injury and investigated I/R‐induced leukocyte migration by intravital microscopy in mouse cremasteric venules. In the kidney model, mice were subjected to an acute bi‐lateral renal ischemia (30 min) followed by a 24hr reperfusion period after which kidneys were removed and PMN infiltration was quantified in tissue sections by immunohistochemistry. Kidneys subjected to I/R injury exhibited a significant PMN infiltration response as compared to sham‐operated kidneys (~22 fold increase) and mice pre‐treated with sJAM‐C (3mg/kg, i.v.) showed a significant reduction in PMN infiltration (49.6% inhibition, p<0.05). In cremasteric venules, sJAM‐C suppressed I/R‐induced (30min ischemia/120 min reperfusion) leukocyte adhesion and transmigration. The results demonstrate a role for JAM‐C in PMN migration as induced by I/R injury.Funded by The Wellcome Trust and The British Heart Foundation.