title: Kupffer cell-monocyte communication is essential for initiating murine liver progenitor cell-mediated liver regeneration.
abstract: Liver progenitor cells (LPCs) are necessary for repair in chronic liver disease because the remaining hepatocytes cannot replicate. However, LPC numbers also correlate with disease severity and hepatocellular carcinoma risk. Thus, the progenitor cell response in diseased liver may be regulated to optimize liver regeneration and minimize the likelihood of tumorigenesis. How this is achieved is currently unknown. Human and mouse diseased liver contain two subpopulations of macrophages with different ontogenetic origins: prenatal yolk sac-derived Kupffer cells and peripheral blood monocyte-derived macrophages. We examined the individual role(s) of Kupffer cells and monocyte-derived macrophages in the induction of LPC proliferation using clodronate liposome deletion of Kupffer cells and adoptive transfer of monocytes, respectively, in the choline-deficient, ethionine-supplemented diet model of liver injury and regeneration. Clodronate liposome treatment reduced initial liver monocyte numbers together with the induction of injury and LPC proliferation. Adoptive transfer of monocytes increased the induction of liver injury, LPC proliferation, and tumor necrosis factor-α production.
  
  
  CONCLUSIONS
  Kupffer cells control the initial accumulation of monocyte-derived macrophages. These infiltrating monocytes are in turn responsible for the induction of liver injury, the increase in tumor necrosis factor-α, and the subsequent proliferation of LPCs.
authors.affiliation: School of Chemistry and Biochemistry, The University of Western Australia, Crawley, Western Australia, Australia.|School of Biomedical Sciences, CHIRI Biosciences Research Precinct, Curtin University, Bentley, Western Australia, Australia.
authors.forename: Caryn L
authors.initials: CL
authors.lastname: Elsegood
authors.affiliation: School of Medicine and Pharmacology, The University of Western Australia, Fremantle, Western Australia, Australia.|School of Biological Sciences and Biotechnology, Murdoch University, Murdoch, Western Australia, Australia.
authors.forename: Chun Wei
authors.initials: CW
authors.lastname: Chan
authors.affiliation: Immunology and Virology Program, Centre for Ophthalmology and Visual Science, The University of Western Australia, Nedlands, Western Australia, Australia.|Centre for Experimental Immunology, Lions Eye Institute, Nedlands, Western Australia, Australia.
authors.forename: Mariapia A
authors.initials: MA
authors.lastname: Degli-Esposti
authors.affiliation: Immunology and Virology Program, Centre for Ophthalmology and Visual Science, The University of Western Australia, Nedlands, Western Australia, Australia.|Centre for Experimental Immunology, Lions Eye Institute, Nedlands, Western Australia, Australia.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Wikstrom
authors.affiliation: School of Biomedical Sciences, CHIRI Biosciences Research Precinct, Curtin University, Bentley, Western Australia, Australia.
authors.forename: Alice
authors.initials: A
authors.lastname: Domenichini
authors.affiliation: School of Biomedical Sciences, CHIRI Biosciences Research Precinct, Curtin University, Bentley, Western Australia, Australia.|Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands and Centre for Medical Research, The University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Kyren
authors.initials: K
authors.lastname: Lazarus
authors.affiliation: Department of Molecular Cell Biology, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.affiliation: Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands and Centre for Medical Research, The University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Ruth
authors.initials: R
authors.lastname: Ganss
authors.affiliation: School of Biomedical Sciences, CHIRI Biosciences Research Precinct, Curtin University, Bentley, Western Australia, Australia.|Department of Gastroenterology and Hepatology, Fiona Stanley and Fremantle Hospitals, South Metropolitan Health Service, Western Australia, Australia.|Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia.
authors.forename: John K
authors.initials: JK
authors.lastname: Olynyk
authors.affiliation: School of Chemistry and Biochemistry, The University of Western Australia, Crawley, Western Australia, Australia.|Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands and Centre for Medical Research, The University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: George C T
authors.initials: GC
authors.lastname: Yeoh
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D007728:Kupffer Cells / Q000502:physiology*; D008099:Liver / Q000166:cytology*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology*