Leukocyte transmigration in inflamed liver: A role for endothelial cell-selective adhesion molecule.
OBJECTIVE
This study was designed to investigate the role of endothelial cell-selective adhesion molecule (ESAM), a recently discovered receptor expressed in endothelial tight junctions and platelets, for leukocyte migration in inflamed liver.


METHODS
The role of ESAM for leukocyte migration in the liver was analyzed using ESAM-deficient mice in a model of warm hepatic ischemia-reperfusion (90min/30-360min).


RESULTS
As shown by immunostaining, ESAM is expressed in sinusoids as well as in venules and is not upregulated upon I/R. Emigrated leukocytes were quantified in tissue sections. Postischemic neutrophil transmigration was significantly attenuated in ESAM-/- mice after 2h of reperfusion, whereas it was completely restored after 6h. In contrast, T-cell migration did not differ between ESAM+/+ and ESAM-/- mice. Using intravital microscopy, we demonstrate that ESAM deficiency attenuates I/R-induced vascular leakage after 30min of reperfusion. The I/R-induced elevation in AST/ALT activity, the sinusoidal perfusion failure, and the number of TUNEL-positive hepatocytes were comparable between ESAM+/+ and ESAM-/- mice.


CONCLUSIONS
ESAM is expressed in the postischemic liver and mediates neutrophil but not T-cell transmigration during early reperfusion. ESAM deficiency attenuates I/R-induced vascular leakage and does not affect leukocyte adherence. Despite the effect on neutrophil migration, ESAM-deficiency does not protect from I/R-induced injury.
Khandoga
Andrej
A
Department of Surgery, Ludwig-Maximilians-Universität München, Marchioninistr. 15, D-81377 Munich, Germany. Andrej.Khandoga@med.uni-muenchen.de
Huettinger
Stefanie
S
Khandoga
Alexander G
AG
Li
Hang
H
Butz
Stefan
S
Jauch
Karl-Walter
KW
Vestweber
Dietmar
D
Krombach
Fritz
F
D000818:Animals; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D003433:Crosses, Genetic; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006098:Granulocytes / Q000201:enzymology; D007249:Inflammation / Q000097:blood* / Q000503:physiopathology; D017493:Leukocyte Common Antigens / Q000032:analysis; D007958:Leukocyte Count; D008099:Liver / Q000503:physiopathology; D008102:Liver Circulation / Q000502:physiology*; D008107:Liver Diseases / Q000097:blood* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008833:Microcirculation / Q000502:physiology; D009283:Naphthol AS D Esterase / Q000097:blood
D015815:Cell Adhesion Molecules; C428190:Esam protein, mouse; D009283:Naphthol AS D Esterase; D017493:Leukocyte Common Antigens