TY - JOUR
T1 - L-selectin and ICAM-1 mediate reperfusion injury and neutrophil adhesion in the warm ischemic mouse liver
AU - Yadav, Surinder S.
AU - Howell, David N.
AU - Gao, Wenshi
AU - Steeber, Douglas A.
AU - Harland, Robert C.
AU - Clavien, Pierre Alain
PY - 1998
Y1 - 1998
N2 - Leukocytes recruited during ischemia-reperfusion to the liver are important mediators of injury. However, the mechanisms of leukocyte adhesion and the role of adhesion receptors in hepatic vasculature remain elusive. L- selectin may critically contribute to injury, priming adhesion for later action of intercellular adhesion molecule-1 (ICAM-1). Paired experiments were performed using mutant mice (L-selectin -/-, ICAM-1 -/-, and L-selectin/ICAM- 1 -/-) and wild-type mice (C57BL/6) to investigate leukocyte adhesion in the ischemic liver. Leukocyte adhesion and infiltration were assessed histologically. Aspartate aminotransferase levels were significantly reduced (2- to 3-fold) in mutant vs. wild-type mice in most groups but most significantly after 90 min of partial hepatic ischemia. Leukocyte adhesion was significantly reduced in all mutant mice. Areas of microcirculatory failure, visualized by intravital microscopy, were prevalent in wild-type but virtually absent in L-selectin-deficient mice. After total hepatic ischemia for 75 or 90 min, survival was better in mutant L-selectin and L- selectin/ICAM-1 mice vs. wild-type mice and ICAM-1 mutants. In conclusion, L- selectin is critical in the pathogenesis of hepatic ischemia-reperfusion injury. Poor sinusoidal perfusion due to leukocyte adhesion and clot formation is a factor of injury and appears to involve L-selectin and ICAM-1 receptors.
AB - Leukocytes recruited during ischemia-reperfusion to the liver are important mediators of injury. However, the mechanisms of leukocyte adhesion and the role of adhesion receptors in hepatic vasculature remain elusive. L- selectin may critically contribute to injury, priming adhesion for later action of intercellular adhesion molecule-1 (ICAM-1). Paired experiments were performed using mutant mice (L-selectin -/-, ICAM-1 -/-, and L-selectin/ICAM- 1 -/-) and wild-type mice (C57BL/6) to investigate leukocyte adhesion in the ischemic liver. Leukocyte adhesion and infiltration were assessed histologically. Aspartate aminotransferase levels were significantly reduced (2- to 3-fold) in mutant vs. wild-type mice in most groups but most significantly after 90 min of partial hepatic ischemia. Leukocyte adhesion was significantly reduced in all mutant mice. Areas of microcirculatory failure, visualized by intravital microscopy, were prevalent in wild-type but virtually absent in L-selectin-deficient mice. After total hepatic ischemia for 75 or 90 min, survival was better in mutant L-selectin and L- selectin/ICAM-1 mice vs. wild-type mice and ICAM-1 mutants. In conclusion, L- selectin is critical in the pathogenesis of hepatic ischemia-reperfusion injury. Poor sinusoidal perfusion due to leukocyte adhesion and clot formation is a factor of injury and appears to involve L-selectin and ICAM-1 receptors.
KW - Gene-targeted deficient mice
KW - Hepatic ischemia-reperfusion injury
KW - No reflow
KW - Survival
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U2 - 10.1152/ajpgi.1998.275.6.g1341
DO - 10.1152/ajpgi.1998.275.6.g1341
M3 - Article
C2 - 9843771
AN - SCOPUS:0032427071
SN - 0363-6143
VL - 275
SP - G1341-G1352
JO - American Journal of Physiology
JF - American Journal of Physiology
IS - 6 38-6
ER -