PMID- 20561705
OWN - NLM
STAT- MEDLINE
DCOM- 20101207
LR  - 20171116
IS  - 1600-0641 (Electronic)
IS  - 0168-8278 (Linking)
VI  - 53
IP  - 3
DP  - 2010 Sep
TI  - Invading macrophages play a major role in the liver progenitor cell response to 
      chronic liver injury.
PG  - 500-7
LID - 10.1016/j.jhep.2010.04.010 [doi]
AB  - BACKGROUND & AIMS: Although a strong association between liver progenitor cells 
      (LPCs) and inflammation exists in many chronic liver diseases, the exact role of 
      the immune system in LPC-mediated hepatic regeneration remains unclear. A number 
      of pro-inflammatory factors were identified in cytokine knockout mice in which 
      the LPC response was attenuated but neither the mechanism nor the producing cells 
      are known. METHODS: To identify the critical immune cells and cytokines required 
      in the LPC response, we compared two diet-induced models of liver injury with two 
      recently established transgenic models of immune-mediated hepatitis. RESULTS: 
      Despite severe inflammation being observed in all models, the generation of LPCs 
      was highly dependent on the cause and kinetics of liver damage. The LPC response 
      was associated with an increase of macrophages and CD8(+) T cells but not natural 
      killer cells. T cell-deficient mice were able to mount a LPC response, albeit 
      delayed, suggesting that T cells are not essential. Mice mounting an LPC response 
      showed elevated numbers of Kupffer cells and invading CX(3)CR1(high)CCR2(high) 
      macrophages secreting persistent high levels of tumour necrosis factor alpha 
      (TNFalpha), a major cytokine involved in the LPC response. CONCLUSIONS: Liver 
      macrophages are an important determinant of LPC expansion during liver 
      regeneration in models of diet- and immune-mediated liver injury. Invading 
      macrophages in particular provide pro-mitogenic cytokines such as TNFalpha that 
      underpin the process. LPC themselves are a source of chemokines (CCL2, CX(3)CL1) 
      that attract infiltrating macrophages.
CI  - Copyright 2010 European Association for the Study of the Liver. Published by 
      Elsevier B.V. All rights reserved.
FAU - Viebahn, Cornelia S
AU  - Viebahn CS
AD  - School of Biomedical, Biomolecular and Chemical Sciences, The University of 
      Western Australia, Australia. connyviebahn@web.de
FAU - Benseler, Volker
AU  - Benseler V
FAU - Holz, Lauren E
AU  - Holz LE
FAU - Elsegood, Caryn L
AU  - Elsegood CL
FAU - Vo, Michelle
AU  - Vo M
FAU - Bertolino, Patrick
AU  - Bertolino P
FAU - Ganss, Ruth
AU  - Ganss R
FAU - Yeoh, George C T
AU  - Yeoh GC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100526
PL  - Netherlands
TA  - J Hepatol
JT  - Journal of hepatology
JID - 8503886
RN  - 0 (CX3C Chemokine Receptor 1)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Cx3cr1 protein, mouse)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - CD8-Positive T-Lymphocytes/immunology/pathology
MH  - CX3C Chemokine Receptor 1
MH  - Chronic Disease
MH  - Diet/adverse effects
MH  - Disease Models, Animal
MH  - Hepatocytes/*pathology
MH  - Liver Diseases/etiology/genetics/*immunology/*pathology
MH  - Liver Regeneration/genetics/immunology
MH  - Macrophages/*immunology/*pathology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Nude
MH  - Mice, Transgenic
MH  - RNA, Messenger/genetics/metabolism
MH  - Receptors, CCR2/metabolism
MH  - Receptors, Chemokine/metabolism
MH  - Stem Cells/*pathology
MH  - Tumor Necrosis Factor-alpha/genetics/metabolism
EDAT- 2010/06/22 06:00
MHDA- 2010/12/14 06:00
CRDT- 2010/06/22 06:00
PHST- 2009/11/17 00:00 [received]
PHST- 2010/03/02 00:00 [revised]
PHST- 2010/04/02 00:00 [accepted]
PHST- 2010/06/22 06:00 [entrez]
PHST- 2010/06/22 06:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
AID - S0168-8278(10)00457-5 [pii]
AID - 10.1016/j.jhep.2010.04.010 [doi]
PST - ppublish
SO  - J Hepatol. 2010 Sep;53(3):500-7. doi: 10.1016/j.jhep.2010.04.010. Epub 2010 May 
      26.