Hepatic reticuloendothelial system dysfunction after ischemia-reperfusion: Role of P-selectin-mediated neutrophil accumulation

Nobuaki Sakamoto, Zhaoli Sun, Matthew L. Brengman, Korsei Maemura, Michitaka Ozaki, Gregory B. Bulkley, Andrew S. Klein

Research output: Contribution to journalArticlepeer-review

Abstract

The relationship between hepatic ischemia-reperfusion (I-R) and subsequent injury through neutrophil accumulation is well described. Although alterations in reticuloendothelial system (RES) function (specifically Kupffer cell function) after I-R have been delineated, the degree to which discrete components of RES function (phagocytosis and killing) are independently modulated under these conditions has not been quantified. A hepatic segmental I-R model was established in mice, in which blood supply to the left lateral lobe of the liver was occluded for 45 minutes, the liver was reperfused, and the laparotomy incision was closed. Experimental animals were pretreated with either vinblastin (1.5 mg/kg) to induce neutropenia or anti-P-selectin monoclonal antibody (mAb; 50 μg/mice) 4 days and 5 minutes before ischemia, respectively. We previously reported that after intravenous injection of chromium 51 (51Cr) and iodine 125 (125I) double-labeled Escherichia coli, hepatic 51Cr levels could be used to reliably quantify hepatic phagocytic clearance (HPC) of bacteria from blood, whereas the subsequent release of 125I from the liver accurately paralleled hepatic bacterial killing efficiency (HKE). Using this double-label bacteria clearance assay, HPC and HKE were depressed after I-R, in association with hepatic neutrophil accumulation. Segmental I-R resulted in decreased HPC and HKE activity in both ischemic and nonischemic hepatic lobes. Depressions in HPC and HKE were attenuated by either vinblastin-induced neutropenia or blocking neutrophil adhesion to the hepatic endothelium with anti-P-selectin mAb. These findings support the hypothesis that I-R induces hepatic RES dysfunction, at least in part, through P-selectin-mediated neutrophil accumulation.

Original languageEnglish (US)
Pages (from-to)940-948
Number of pages9
JournalLiver Transplantation
Volume9
Issue number9
DOIs
StatePublished - Sep 1 2003

ASJC Scopus subject areas

  • Surgery
  • Hepatology
  • Transplantation

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