JAM-A-Defizienz verstärkt den hepatischen Ischämie- Reperfusionsschaden trotz Verminderung der transendothelialen Migration von Leukozyten

The endothelial receptors that control leukocyte transmigration in the postischemic liver are not identified. Here, we tested the hypothesis that junctional adhesion molecule-A (JAM-A) is involved in leukocyte transmigration during hepatic ischemia-reperfusion (I/R). In wild-type, JAM-A-/-, and endothelial JAM-A-/- mice, leukocyte rolling and adhesion were quantified in venules and sinusoids using intravital microscopy after I/R and under control conditions. Leukocyte transmigration into the perivascular space was analyzed using tissue staining for CD45. In wild-type mice, I/R induced enhanced leukocyte rolling and adherence as well as leukocyte transmigration as compared to the sham-operated group. In JAM-A-/- mice, postischemic leukocyte rolling remained unaffected, whereas the number of adherent leukocytes was increased by 40%. Leukocyte transmigration was significantly attenuated in both JAM-A-/- mice and endothelial JAM-A-/- mice. JAM-A expression was detected in hepatic venules but not in sinusoids. Interestingly, the I/R-induced increases in ALT/ AST activity and sinusoidal perfusion failure were not reduced in JAM-A-/- mice, and the number of TUNEL-positive hepatocytes was even significantly higher. In conclusion, we show for the first time that JAM-A is expressed in the vessel wall of hepatic venules and serves as an endothelial receptor controlling leukocyte transmigration, but does not mediate leukocyte rolling and adhesion in the postischemic liver. The fact that apoptotic injury was more severe in JAM-A-/- mice might point to a role of transmigrated leukocytes in the process of tissue remodeling after I/R.