title: Contrasting responses of Kupffer cells and inflammatory mononuclear phagocytes to biliary obstruction in a mouse model of cholestatic liver injury.
abstract: BACKGROUND
  Biliary obstruction and cholestasis are serious complications of many liver diseases. Although resident hepatic macrophages (Kupffer cells) are frequently implicated in disease progression, most studies fail to differentiate the contribution of Kupffer cells and inflammatory mononuclear phagocytes (iMNPs) that infiltrate the liver subsequent to obstruction.
  
  
  OBJECTIVE
  This study was undertaken to examine the roles and potential interactions of these two disparate mononuclear phagocyte populations in hepatic injury attending cholestasis.
  
  
  METHODS
  Female, C57Bl/6 mice were injected with magnetic beads on day 3 prior to sham operation or bile duct ligation (BDL) to facilitate subsequent Kupffer cell isolation. Three days post-surgery, animals were euthanized, and bead-containing Kupffer cells and iMNPs were separated, purified and analysed. To examine the ability of Kupffer cells to modulate iMNP activity, iMNPs were isolated from the livers of intact and Kupffer cell-depleted mice on day 3 post-surgery and compared.
  
  
  RESULTS
  Purified Kupffer cells and iMNP populations obtained from BDL mice exhibited heterogeneous morphologies rendering them visually indistinguishable. iMNPs, however, were characterized by the increased expression of Ly-6C and CD11b and the elevated production of chemokines/cytokines characteristic of inflammatory cells. In the absence of Kupffer cells, iMNPs immigrating to the liver following BDL exhibited significant decreases in CD11b and Ly-6C expression, and in pro-inflammatory chemokine/cytokine production.
  
  
  CONCLUSIONS
  Kupffer cells and iMNPs exhibit disparate biological responses to biliary obstruction and cholestasis. Kupffer cells play a key role in regulating iMNP influx and activity.
authors.affiliation: Department of Medicine, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, RI 02903, USA.
authors.forename: Caroline C
authors.initials: CC
authors.lastname: Duwaerts
authors.forename: Stephan
authors.initials: S
authors.lastname: Gehring
authors.forename: Chao-Wen
authors.initials: CW
authors.lastname: Cheng
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Gregory
mesh_terms: D000818:Animals; D002780:Cholestasis, Intrahepatic / Q000503:physiopathology*; D005260:Female; D005434:Flow Cytometry; D007728:Kupffer Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012157:Mononuclear Phagocyte System / Q000503:physiopathology*; D060888:Real-Time Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms