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P-selectin glycoprotein ligand-1-mediated leukocyte recruitment regulates hepatocellular damage in acute obstructive cholestasis in mice.

Dold, Stefan LU ; Laschke, Matthias LU ; Zhau, Yilin; Schilling, Martin; Menger, Michael; Jeppsson, Bengt LU and Thorlacius, Henrik LU (2010) In Inflammation Research1995-01-01+01:00 59. p.291-298
Abstract
OBJECTIVE: Leukocytes mediate hepatocellular injury in obstructive cholestasis. The aim of the present study was to define the role of P-selectin glycoprotein ligand-1 (PSGL-1) in cholestasis-induced leukocyte recruitment and liver damage. METHODS: C57BL/6 mice were pre-treated with an anti-PSGL-1 antibody or a control antibody prior to bile duct ligation (BDL) for 12 h. Hepatic recruitment of leukocytes and sinusoidal perfusion were determined by means of intravital fluorescence microscopy. Liver damage was monitored by measuring serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Hepatic levels of CXC chemokines were determined by ELISA. RESULTS: BDL caused significant hepatocellular damage indicated by... (More)
OBJECTIVE: Leukocytes mediate hepatocellular injury in obstructive cholestasis. The aim of the present study was to define the role of P-selectin glycoprotein ligand-1 (PSGL-1) in cholestasis-induced leukocyte recruitment and liver damage. METHODS: C57BL/6 mice were pre-treated with an anti-PSGL-1 antibody or a control antibody prior to bile duct ligation (BDL) for 12 h. Hepatic recruitment of leukocytes and sinusoidal perfusion were determined by means of intravital fluorescence microscopy. Liver damage was monitored by measuring serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Hepatic levels of CXC chemokines were determined by ELISA. RESULTS: BDL caused significant hepatocellular damage indicated by increased serum activities of ALT and AST as well as decreased sinusoidal perfusion and clear-cut hepatic infiltration of leukocytes. Administration of the anti-PSGL-1 antibody reduced BDL-induced levels of ALT by 78% and AST by 77%. Inhibition of PSGL-1 decreased BDL-provoked leukocyte rolling and adhesion in post-sinusoidal venules by more than 81%. Moreover, we found that immunoneutralisation of PSGL-1 restored sinusoidal perfusion and decreased hepatic formation of CXC chemokines in cholestatic mice. CONCLUSIONS: Our novel data show that PSGL-1 plays an important role in cholestatic liver damage by regulating leukocyte rolling in post-sinusoidal venules. Consequently, interference with PSGL-1 attenuates cholestasis-provoked leukocyte adhesion and extravasation in the liver. Thus, inhibition of PSGL-1 may help to protect against hepatocellular damage in cholestatic diseases. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Inflammation Research1995-01-01+01:00
volume
59
pages
291 - 298
publisher
Birkhaüser
external identifiers
  • wos:000275421400006
  • pmid:19826766
  • scopus:77953057085
ISSN
1420-908X
DOI
10.1007/s00011-009-0099-2
language
English
LU publication?
yes
id
452db68b-f176-4203-912a-7ab36c85e0e8 (old id 1500365)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19826766?dopt=Abstract
date added to LUP
2009-11-03 15:12:52
date last changed
2018-05-29 10:50:26
@article{452db68b-f176-4203-912a-7ab36c85e0e8,
  abstract     = {OBJECTIVE: Leukocytes mediate hepatocellular injury in obstructive cholestasis. The aim of the present study was to define the role of P-selectin glycoprotein ligand-1 (PSGL-1) in cholestasis-induced leukocyte recruitment and liver damage. METHODS: C57BL/6 mice were pre-treated with an anti-PSGL-1 antibody or a control antibody prior to bile duct ligation (BDL) for 12 h. Hepatic recruitment of leukocytes and sinusoidal perfusion were determined by means of intravital fluorescence microscopy. Liver damage was monitored by measuring serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Hepatic levels of CXC chemokines were determined by ELISA. RESULTS: BDL caused significant hepatocellular damage indicated by increased serum activities of ALT and AST as well as decreased sinusoidal perfusion and clear-cut hepatic infiltration of leukocytes. Administration of the anti-PSGL-1 antibody reduced BDL-induced levels of ALT by 78% and AST by 77%. Inhibition of PSGL-1 decreased BDL-provoked leukocyte rolling and adhesion in post-sinusoidal venules by more than 81%. Moreover, we found that immunoneutralisation of PSGL-1 restored sinusoidal perfusion and decreased hepatic formation of CXC chemokines in cholestatic mice. CONCLUSIONS: Our novel data show that PSGL-1 plays an important role in cholestatic liver damage by regulating leukocyte rolling in post-sinusoidal venules. Consequently, interference with PSGL-1 attenuates cholestasis-provoked leukocyte adhesion and extravasation in the liver. Thus, inhibition of PSGL-1 may help to protect against hepatocellular damage in cholestatic diseases.},
  author       = {Dold, Stefan and Laschke, Matthias and Zhau, Yilin and Schilling, Martin and Menger, Michael and Jeppsson, Bengt and Thorlacius, Henrik},
  issn         = {1420-908X},
  language     = {eng},
  pages        = {291--298},
  publisher    = {Birkhaüser},
  series       = {Inflammation Research1995-01-01+01:00},
  title        = {P-selectin glycoprotein ligand-1-mediated leukocyte recruitment regulates hepatocellular damage in acute obstructive cholestasis in mice.},
  url          = {http://dx.doi.org/10.1007/s00011-009-0099-2},
  volume       = {59},
  year         = {2010},
}