PMID- 26473398
OWN - NLM
STAT- MEDLINE
DCOM- 20160510
LR  - 20220129
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Print)
IS  - 0270-9139 (Linking)
VI  - 63
IP  - 1
DP  - 2016 Jan
TI  - Bidirectional transendothelial migration of monocytes across hepatic sinusoidal 
      endothelium shapes monocyte differentiation and regulates the balance between 
      immunity and tolerance in liver.
PG  - 233-46
LID - 10.1002/hep.28285 [doi]
AB  - Monocytes are versatile cells that can fulfill proinflammatory and 
      anti-inflammatory functions when recruited to the liver. Recruited monocytes 
      differentiate into tissue macrophages and dendritic cells, which sample antigens 
      and migrate to lymph nodes to elicit T-cell responses. The signals that determine 
      monocyte differentiation and the role of hepatic sinusoidal endothelial cells 
      (HSECs) in this process are poorly understood. HSECs are known to modulate T-cell 
      activation, which led us to investigate whether transendothelial migration of 
      monocytes across HSECs influences their phenotype and function. Subsets of 
      blood-derived monocytes were allowed to transmigrate across human HSECs into a 
      collagen matrix. Most migrated cells remained in the subendothelial matrix, but 
      ~10% underwent spontaneous basal to apical transendothelial migration. The 
      maturation, cytokine secretion, and T-cell stimulatory capacity of reverse 
      transmigrating (RT) and subendothelial (SE) monocytes were compared. SE monocytes 
      were mainly CD16(-) , whereas 75%-80% of RT monocytes were CD16(+) . SE monocytes 
      derived from the CD14(++) CD16(-) subset and exhibited high phagocytic activity, 
      whereas RT monocytes originated from CD14(++) CD16(+) and CD14(+) CD16(++) 
      monocytes, displayed an immature dendritic cell-like phenotype (CD11c(pos) 
      HLA-DR(pos) CD80lo CD86lo ), and expressed higher levels of chemokine (C-C motif) 
      receptor 8. Consistent with a dendritic cell phenotype, RT monocytes secreted 
      inflammatory cytokines and induced antigen-specific CD4(+) T-cell activation. In 
      contrast, SE monocytes suppressed T-cell proliferation and activation and 
      exhibited endotoxin tolerance. Transcriptome analysis underscored the functional 
      differences between SE and RT monocytes. CONCLUSIONS: Migration across HSECs 
      shapes the subsequent fate of monocytes, giving rise to anergic macrophage-like 
      cells in tissue and the release of immunocompetent pre-dendritic cells into the 
      circulation.
CI  - (c) 2015 by the American Association for the Study of Liver Diseases.
FAU - Zimmermann, Henning W
AU  - Zimmermann HW
AD  - National Institute for Health Research Biomedical Research Unit and Centre for 
      Liver Research, University of Birmingham, Birmingham, UK.
AD  - Department of Medicine III, University Hospital Aachen, RWTH Aachen University, 
      Aachen, Germany.
FAU - Bruns, Tony
AU  - Bruns T
AD  - National Institute for Health Research Biomedical Research Unit and Centre for 
      Liver Research, University of Birmingham, Birmingham, UK.
AD  - Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller 
      University of Jena, Jena, Germany.
AD  - Center for Sepsis Control and Care, Jena University Hospital, Friedrich Schiller 
      University of Jena, Jena, Germany.
FAU - Weston, Chris J
AU  - Weston CJ
AD  - National Institute for Health Research Biomedical Research Unit and Centre for 
      Liver Research, University of Birmingham, Birmingham, UK.
FAU - Curbishley, Stuart M
AU  - Curbishley SM
AD  - National Institute for Health Research Biomedical Research Unit and Centre for 
      Liver Research, University of Birmingham, Birmingham, UK.
FAU - Liaskou, Evaggelia
AU  - Liaskou E
AD  - National Institute for Health Research Biomedical Research Unit and Centre for 
      Liver Research, University of Birmingham, Birmingham, UK.
FAU - Li, Ka-Kit
AU  - Li KK
AD  - National Institute for Health Research Biomedical Research Unit and Centre for 
      Liver Research, University of Birmingham, Birmingham, UK.
FAU - Resheq, Yazid J
AU  - Resheq YJ
AD  - National Institute for Health Research Biomedical Research Unit and Centre for 
      Liver Research, University of Birmingham, Birmingham, UK.
AD  - Department of Internal Medicine 5, Hematology and Oncology, University of 
      Erlangen-Nuremberg, Erlangen, Germany.
FAU - Badenhorst, Paul W
AU  - Badenhorst PW
AD  - School of Immunity and Infection, University of Birmingham, Birmingham, UK.
FAU - Adams, David H
AU  - Adams DH
AD  - National Institute for Health Research Biomedical Research Unit and Centre for 
      Liver Research, University of Birmingham, Birmingham, UK.
LA  - eng
GR  - Wellcome Trust/United Kingdom
GR  - G0700301/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151123
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
SB  - IM
MH  - *Cell Differentiation
MH  - Cells, Cultured
MH  - Endothelium/cytology
MH  - Humans
MH  - *Immune Tolerance
MH  - Liver/*cytology/*immunology
MH  - Monocytes/*physiology
MH  - Transendothelial and Transepithelial Migration/*physiology
PMC - PMC6016741
MID - EMS78107
EDAT- 2015/10/17 06:00
MHDA- 2016/05/11 06:00
CRDT- 2015/10/17 06:00
PHST- 2015/05/26 00:00 [received]
PHST- 2015/09/29 00:00 [revised]
PHST- 2015/10/09 00:00 [accepted]
PHST- 2015/10/17 06:00 [entrez]
PHST- 2015/10/17 06:00 [pubmed]
PHST- 2016/05/11 06:00 [medline]
AID - 10.1002/hep.28285 [doi]
PST - ppublish
SO  - Hepatology. 2016 Jan;63(1):233-46. doi: 10.1002/hep.28285. Epub 2015 Nov 23.