Journal
SURGERY
Volume 144, Issue 3, Pages 385-393Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.surg.2008.05.010
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Funding
- Swedish Medical Research Council [2006-4889]
- Crafoordska Stiftelsen
- Einar och Inga Nilssons stiftelse
- Harald och Greta Jaenssons stiftelse
- Greta och Johan Kocks stiftelser
- Froken Agnes Nilssons stiftelse
- Franke och Margareta Bergqvists stiftelse framjande av cancerforskning
- Magnus Bergvulls stiftelse
- Mossfelts stiftelse
- Nanna Svartz stiftelse
- Ruth och Richard Julins stiftelse
- Svenska Lakaresallskapet
- Allmana sjukhusets i Malmo stiftelse for bekampande av cancer
- MAS fonder
- Malmo University Hospital
- Lund University
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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 LEA-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 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.
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