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Cholestatic liver damage is mediated by lymphocyte function antigen-1-dependent recruitment of leukocytes.

Dold, Stefan LU ; Laschke, Matthias W; Lavasani, Shahram LU ; Menger, Michael D and Thorlacius, Henrik LU (2008) In Surgery 144(3). p.385-393
Abstract
BACKGROUND: The role of specific adhesion molecules in cholestasis-induced leukocyte recruitment in the liver is not known. Therefore, the aim of our experimental study was to evaluate the role of lymphocyte function antigen-1 (LFA-1) in cholestatic liver injury. METHODS: C57BL/6 mice underwent bile duct ligation for 12 hours. Mice were pretreated with an anti-LFA-1 antibody or control antibody. Subsequently, hepatic accumulation of leukocytes and sinusoidal perfusion were determined by means of intravital fluorescence microscopy. Hepatocellular damage was monitored by measuring serum levels of alanine aminotransferase and aspartate aminotransferase. CXC chemokines in the liver were determined by enzyme-linked immunosorbent assay. RESULTS:... (More)
BACKGROUND: The role of specific adhesion molecules in cholestasis-induced leukocyte recruitment in the liver is not known. Therefore, the aim of our experimental study was to evaluate the role of lymphocyte function antigen-1 (LFA-1) in cholestatic liver injury. METHODS: C57BL/6 mice underwent bile duct ligation for 12 hours. Mice were pretreated with an anti-LFA-1 antibody or control antibody. Subsequently, hepatic accumulation of leukocytes and sinusoidal perfusion were determined by means of intravital fluorescence microscopy. Hepatocellular damage was monitored by measuring serum levels of alanine aminotransferase and aspartate aminotransferase. CXC chemokines in the liver were determined by enzyme-linked immunosorbent assay. RESULTS: Bile duct ligation provoked clear-cut recruitment of leukocytes and liver damage, as indicated by increased serum activities of liver enzymes and sinusoidal perfusion failure. Neutrophils expressed greater levels of LFA-1 and inhibition of LFA-1 significantly decreased serum activity of alanine aminotransferase and aspartate aminotransferase levels in cholestatic mice. Immunoneutralization of LFA-1 reduced leukocyte adhesion in postsinusoidal venules that had been induced by bile duct ligation, whereas leukocyte rolling and sinusoidal accumulation were not changed. Moreover, blocking LFA-1 function restored sinusoidal perfusion in cholestatic animals. CONCLUSION: These findings demonstrate an important role of LFA-1 in supporting cholestasis-induced leukocyte recruitment in the liver. Thus, targeting LFA-1 may help to protect against pathologic inflammation and liver damage in cholestatic liver diseases. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Surgery
volume
144
issue
3
pages
385 - 393
publisher
Elsevier
external identifiers
  • WOS:000258743500004
  • PMID:18707037
  • Scopus:49249120754
ISSN
1532-7361
DOI
10.1016/j.surg.2008.05.010
language
English
LU publication?
yes
id
1a2b40ef-19a2-4118-ac11-1c6ddf8db580 (old id 1223169)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18707037?dopt=Abstract
date added to LUP
2008-09-02 14:33:19
date last changed
2016-10-13 04:24:56
@misc{1a2b40ef-19a2-4118-ac11-1c6ddf8db580,
  abstract     = {BACKGROUND: The role of specific adhesion molecules in cholestasis-induced leukocyte recruitment in the liver is not known. Therefore, the aim of our experimental study was to evaluate the role of lymphocyte function antigen-1 (LFA-1) in cholestatic liver injury. METHODS: C57BL/6 mice underwent bile duct ligation for 12 hours. Mice were pretreated with an anti-LFA-1 antibody or control antibody. Subsequently, hepatic accumulation of leukocytes and sinusoidal perfusion were determined by means of intravital fluorescence microscopy. Hepatocellular damage was monitored by measuring serum levels of alanine aminotransferase and aspartate aminotransferase. CXC chemokines in the liver were determined by enzyme-linked immunosorbent assay. RESULTS: Bile duct ligation provoked clear-cut recruitment of leukocytes and liver damage, as indicated by increased serum activities of liver enzymes and sinusoidal perfusion failure. Neutrophils expressed greater levels of LFA-1 and inhibition of LFA-1 significantly decreased serum activity of alanine aminotransferase and aspartate aminotransferase levels in cholestatic mice. Immunoneutralization of LFA-1 reduced leukocyte adhesion in postsinusoidal venules that had been induced by bile duct ligation, whereas leukocyte rolling and sinusoidal accumulation were not changed. Moreover, blocking LFA-1 function restored sinusoidal perfusion in cholestatic animals. CONCLUSION: These findings demonstrate an important role of LFA-1 in supporting cholestasis-induced leukocyte recruitment in the liver. Thus, targeting LFA-1 may help to protect against pathologic inflammation and liver damage in cholestatic liver diseases.},
  author       = {Dold, Stefan and Laschke, Matthias W and Lavasani, Shahram and Menger, Michael D and Thorlacius, Henrik},
  issn         = {1532-7361},
  language     = {eng},
  number       = {3},
  pages        = {385--393},
  publisher    = {ARRAY(0xa7b88c0)},
  series       = {Surgery},
  title        = {Cholestatic liver damage is mediated by lymphocyte function antigen-1-dependent recruitment of leukocytes.},
  url          = {http://dx.doi.org/10.1016/j.surg.2008.05.010},
  volume       = {144},
  year         = {2008},
}