title: Neutrophil-mediated sinusoidal endothelial cell injury after extensive hepatectomy in cholestatic rats.
abstract: The aim of this study was to assess the hypothesis that hepatic failure after extensive hepatectomy in patients with obstructive jaundice (OJ) may be mediated by polymorphonuclear neutrophils (PMN). In the OJ group, rats underwent a partial hepatectomy of 78% after 2 weeks of cholestasis and subsequent external biliary drainage for 5 days. In the sham-operated control group, rats were partially hepatectomized 19 days after the sham surgery. The concentration of the serum cytokine-induced neutrophil chemoattractant (CINC), which is homologous with the growth-related oncogene (gro) product, a member of the human interleukin (IL)-8 family, and a major neutrophil chemotactic factor in rats, increased concomitantly with accumulation of PMNs in the hepatic sinusoids during cholestasis and subsequent external drainage. However, changes in the serum purine nucleoside phosphorylase (PNP)/alanine transaminase (ALT) ratio as a marker of sinusoidal endothelial cell (SEC) injury showed no significant differences between the two groups. Intercellular adhesion molecule-1 (ICAM-1) expression on SECs was not affected by cholestasis and external drainage. After partial hepatectomy, the serum CINC concentration immediately elevated more prominently in the OJ group than in the sham-operated control group, and accumulation of PMNs in the sinusoids was more obvious and prolonged in the former. ICAM-1 expression was enhanced in both groups with a peak between 24 and 48 hours after partial hepatectomy. At this peak period, a significantly higher PNP/ALT ratio was observed in the OJ group. These results suggest that accumulation of PMNs in the sinusoidal space and ICAM-1 expression on SECs might be closely associated with the development of SEC injury after extensive hepatectomy in cholestasis.
authors.affiliation: First Department of Surgery, School of Medicine, Chiba University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ohtsuka
authors.forename: M
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Y
authors.initials: Y
authors.lastname: Kondo
authors.forename: N
authors.initials: N
authors.lastname: Nakajima
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000097:blood; D002779:Cholestasis / Q000097:blood / Q000150:complications / Q000601:surgery*; D004727:Endothelium / Q000201:enzymology / Q000473:pathology; D006133:Growth Substances / Q000097:blood; D006498:Hepatectomy / Q000009:adverse effects*; D006501:Hepatic Encephalopathy / Q000209:etiology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008297:Male; D018375:Neutrophil Activation / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C513297:Cxcl1 protein, rat; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D018799:Intercellular Adhesion Molecule-1; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase