title: Mechanism of neutrophil accumulation in sinusoids after extrahepatic biliary obstruction.
abstract: OBJECTIVE
  Polymorphonuclear neutrophil (PMN) infiltration represents a potential source of liver injury, but the precise mechanisms of PMN infiltration in cholestatic liver are not fully understood.
  
  
  METHODS
  This study investigated hepatic expression of cytokine-induced neutrophil chemoattractant (CINC) 14 days after bile duct ligation, as well as the number of infiltrated PMNs in livers. Portal venous endotoxin levels were also evaluated. Furthermore, in vitro CINC production by isolated liver cells from obstructive jaundice (OJ) liver or sham-treated liver was evaluated after stimulation with tumor necrosis factor-alpha (TNFalpha), interleukin-1beta (IL-1beta) or LPS.
  
  
  RESULTS
  The number of infiltrated PMNs in sinusoids significantly increased in OJ liver, as compared to sham-treated liver. CINC mRNA expression was also increased in OJ liver. Immunohistochemical study revealed that the majority of the CINC-positive cells were hepatocytes. In vitro study proved that CINC production by isolated hepatocytes was markedly enhanced by IL-1beta stimulation in OJ liver. Furthermore, IL-1beta production by LPS-stimulated Kupffer cells isolated from OJ liver was significantly increased, compared to those from sham-treated liver. Portal venous endotoxin was detectable only in OJ rats.
  
  
  CONCLUSIONS
  Excessive production of IL-1beta by activated Kupffer cells, as a result of portal endotoxemia, may play an important role for increased CINC release from hepatocytes in cholestatic liver, leading to PMN infiltration.
authors.affiliation: Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Wakabayashi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimizu
authors.forename: Fumio
authors.initials: F
authors.lastname: Kimura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshidome
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ohtsuka
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kato
authors.forename: Masaru
authors.initials: M
authors.lastname: Miyazaki
mesh_terms: D000818:Animals; D002450:Cell Communication; D018929:Cell Culture Techniques; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D001651:Cholestasis, Extrahepatic / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D053583:Interleukin-1beta / Q000502:physiology; D008297:Male; D018375:Neutrophil Activation / Q000502:physiology; D020556:Neutrophil Infiltration / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D019743:Chemokines, CXC; D053583:Interleukin-1beta; D012333:RNA, Messenger