PMID- 23184590
OWN - NLM
STAT- MEDLINE
DCOM- 20130705
LR  - 20211021
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Linking)
VI  - 57
IP  - 4
DP  - 2013 Apr
TI  - Roles of dendritic cells in murine hepatic warm and liver transplantation-induced 
      cold ischemia/reperfusion injury.
PG  - 1585-96
LID - 10.1002/hep.26129 [doi]
AB  - Dendritic cells (DCs) induce and regulate both innate and adaptive immune 
      responses; however, their in vivo functional importance in hepatic 
      ischemia/reperfusion (IR) injury is perplexing. We hypothesized that 
      liver-resident DC and locally recruited blood-borne DC might have distinctive 
      roles in hepatic IR injury. We tested this hypothesis by using DC-deficient, 
      fms-like tyrosine kinase 3 ligand (Flt3L) knockout (KO) mice in hepatic warm (70% 
      partial clamping for 60 minutes) and cold IR injury (liver transplant [LTx] with 
      24-hour cold storage). Flt3L KO liver and lymphoid organs contained virtually no 
      CD11c+ F4/80- DC. Hepatic warm IR injury was significantly lower in Flt3L KO than 
      in wildtype (WT) mice with lower alanine aminotransferase (ALT) levels, reduced 
      hepatic necrosis, and lower neutrophil infiltration. Hepatic messenger RNA (mRNA) 
      and protein levels for inflammatory cytokines (tumor necrosis factor alpha 
      [TNFalpha], interleukin [IL]-6) and chemokines (CCL2, CXCL2) were also significantly 
      lower in Flt3L KO than in WT mice, indicating that lack of both liver-resident 
      and blood-borne DC ameliorated hepatic warm IR injury. Adoptive transfer of 
      splenic or hepatic WT DC into Flt3L KO or WT mice increased hepatic warm IR 
      injury, suggesting injurious roles of DC infusion. When Flt3L KO liver was 
      transplanted into WT mice, ALT levels were significantly higher than in WT to WT 
      LTx, with enhanced hepatic necrosis and neutrophil infiltration, indicating a 
      protective role of liver-resident DC. CONCLUSION: Using both warm and cold 
      hepatic IR models, this study suggests differential roles of liver-resident 
      versus blood-borne DC, and points to the importance of the local microenvironment 
      in determining DC function during hepatic IR injury.
CI  - Copyright (c) 2012 American Association for the Study of Liver Diseases.
FAU - Zhang, Matthew
AU  - Zhang M
AD  - Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, 
      PA 15213, USA.
FAU - Ueki, Shinya
AU  - Ueki S
FAU - Kimura, Shoko
AU  - Kimura S
FAU - Yoshida, Osamu
AU  - Yoshida O
FAU - Castellaneta, Antonino
AU  - Castellaneta A
FAU - Ozaki, Kikumi S
AU  - Ozaki KS
FAU - Demetris, Anthony J
AU  - Demetris AJ
FAU - Ross, Mark
AU  - Ross M
FAU - Vodovotz, Yoram
AU  - Vodovotz Y
FAU - Thomson, Angus W
AU  - Thomson AW
FAU - B Stolz, Donna
AU  - B Stolz D
FAU - Geller, David A
AU  - Geller DA
FAU - Murase, Noriko
AU  - Murase N
LA  - eng
GR  - R01DK71753/DK/NIDDK NIH HHS/United States
GR  - P01 AI081678/AI/NIAID NIH HHS/United States
GR  - P01AI81678/AI/NIAID NIH HHS/United States
GR  - R01 DK071753/DK/NIDDK NIH HHS/United States
GR  - T35 DK065521/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (Cytokines)
RN  - 0 (Membrane Proteins)
RN  - 0 (flt3 ligand protein)
RN  - EC 2.6.1.2 (Alanine Transaminase)
SB  - IM
MH  - Alanine Transaminase/metabolism
MH  - Animals
MH  - Cold Ischemia/*adverse effects
MH  - Cytokines/metabolism
MH  - Dendritic Cells/drug effects/*pathology/physiology
MH  - Immunity, Innate
MH  - Liver/metabolism/*pathology
MH  - *Liver Transplantation
MH  - Lymphoid Tissue/pathology/physiology
MH  - Membrane Proteins/deficiency/genetics/pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Models, Animal
MH  - Necrosis
MH  - Reperfusion Injury/*etiology/metabolism/*pathology
MH  - Warm Ischemia/*adverse effects
EDAT- 2012/11/28 06:00
MHDA- 2013/07/06 06:00
CRDT- 2012/11/28 06:00
PHST- 2012/05/07 00:00 [received]
PHST- 2012/10/23 00:00 [accepted]
PHST- 2012/11/28 06:00 [entrez]
PHST- 2012/11/28 06:00 [pubmed]
PHST- 2013/07/06 06:00 [medline]
AID - 10.1002/hep.26129 [doi]
PST - ppublish
SO  - Hepatology. 2013 Apr;57(4):1585-96. doi: 10.1002/hep.26129.