P-Selectin mediates reperfusion injury through neutrophil and platelet sequestration in the warm ischemic mouse liver.
Hepatic damage following ischemia-reperfusion injury involves polymorphonuclear leukocytes (PMN) and platelet sequestration, however the mechanisms of adhesion remain elusive. In this study, using gene-targeted deficient mice, we evaluated P-selectin and its contribution to PMN and platelet adhesion in hepatic damage. In an in vivo warm ischemia model, hepatic injury was assessed by serum transaminase levels, survival, PMN adhesion by histological analysis, and platelet sequestration by immunostaining. Serum transaminase levels were strikingly reduced (by up to threefold) in the P-selectin deficient mice, particularly at 90 minutes of ischemia, when compared with wild-type controls. PMN adhesion and platelet sequestration was also significantly decreased in P-selectin deficient mice following 90 minutes of partial ischemia. Animal survival was significantly improved after 75 minutes of total hepatic ischemia in P-selectin deficient mice when compared with wild-type mice. Survival was also achieved after 90 minutes of ischemia in the mutant mice whereas none of the wild-type animals survived. These data show that P-selectin plays a critical role in PMN and platelet adhesion following ischemia-reperfusion injury to the liver.
Yadav
S S
SS
Hepatobiliary and Liver Transplant Laboratory, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Howell
D N
DN
Steeber
D A
DA
Harland
R C
RC
Tedder
T F
TF
Clavien
P A
PA
D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D007511:Ischemia / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D008099:Liver / Q000473:pathology; D008102:Liver Circulation / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000502:physiology*; D019007:P-Selectin / Q000378:metabolism / Q000502:physiology*; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*; D016019:Survival Analysis; D000637:Transaminases / Q000097:blood
D019007:P-Selectin; D000637:Transaminases