Anti-ICAM-1 blockade reduces postsinusoidal WBC adherence following cold ischemia and reperfusion, but does not improve early graft function in rat liver transplantation.

Abstract:

BACKGROUND/AIM:The present in vivo study investigated the impact of a monoclonal antibody directed against the intercellular adhesion molecule-1 (ICAM-1) on initial microvascular reperfusion injury after liver transplantation. METHODS:Orthotopic, syngeneic liver transplantation including arterial reconstruction was performed in male Lewis rats after 24 h graft storage in University of Wisconsin (UW) solution at 4 degrees C. Animals received either an anti-ICAM-1 antibody (n=7), an IgG1 control antibody (n=8) or saline only (n=7). Hepatic microvascular alterations during the initial 90 min of reperfusion were assessed using intravital fluorescence microscopy. Early graft dysfunction was determined by analysis of bile flow. RESULTS:After treatment with anti-ICAM-1 mAb, hepatic microvascular perfusion was found improved when compared with that of IgG1- and saline-treated controls. In addition, anti-ICAM-1 mAb effectively reduced the number of permanently adherent white blood cells in postsinusoidal venules (284.4+/-59.1 mm(-2) vs IgG1: 371.9+/-26.7 mm(-2) and saline: 431.8+/-46.4 mm(-2); p<0.05). In contrast, the number of stagnant white blood cells in sinusoids was higher (p<0.05) in liver grafts with blocked ICAM-1 (320.6+/-17.2 mm(-2)) compared with that of IgG1- (215.2+/-11.1 mm(-2)) and saline-treated controls (226.4+/-14.0 mm(-2)). Measurement of hepatic uptake of fluorescent-labeled latex particles did not reveal significant differences in phagocytic activity. Finally, bile flow also did not differ between the three groups studied. CONCLUSION:Together these results indicate that ICAM-1 is involved in the process that mediates white blood cells adherence in postsinusoidal venules, whereas in hepatic sinusoids other mechanisms apart from ICAM-1-mediated white blood cells adherence seem to be fundamental for posttransplant white blood cells accumulation. Our data further suggest that white blood cells adherence in postsinusoidal venules via ICAM-1 does not make a major contribution to the pathogenesis of early cold ischemia/reperfusion injury after liver transplantation.

journal_name

J Hepatol

journal_title

Journal of hepatology

authors

Rentsch M,Post S,Palma P,Lang G,Menger MD,Messmer K

doi

10.1016/s0168-8278(00)80252-4

subject

Has Abstract

pub_date

2000-05-01 00:00:00

pages

821-8

issue

5

eissn

0168-8278

issn

1600-0641

pii

S0168-8278(00)80252-4

journal_volume

32

pub_type

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    更新日期:2019-11-01 00:00:00

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    doi:10.1016/s0168-8278(03)00189-2

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    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2006.01.025

    authors: Zografos TA,Rigopoulou EI,Liaskos C,Togousidis E,Zachou K,Gatselis N,Germenis A,Dalekos GN

    更新日期:2006-05-01 00:00:00

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    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/s0168-8278(88)80475-6

    authors: Vickers C,Neuberger J,Buckels J,McMaster P,Elias E

    更新日期:1988-10-01 00:00:00

  • Frequent loss of chromosome 3p and hypermethylation of RASSF1A in cholangiocarcinoma.

    abstract:BACKGROUND/AIMS:Cholangiocarcinoma comprises 5-20% of all primary malignant tumors of the liver. However, the lack of information about the genetic basis of cholangiocarcinoma has impeded characterization and understanding of its biological behavior. METHODS:In this study, genome-wide aberrations in 13 cases of cholan...

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    doi:10.1016/s0168-8278(02)00269-6

    authors: Wong N,Li L,Tsang K,Lai PB,To KF,Johnson PJ

    更新日期:2002-11-01 00:00:00