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Published on: August 13, 2015
Blockage of CX3CL1 Attenuates Platelet and Leukocyte Recruitment in Murine Hepatic I/R
Dominik Funken1,2,3, Alexandra Brüggemann1,2, Konstantin Mende1,2
1Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital of Munich, Ludwig-Maximilians-University of Munich, Munich, Germany.
Insights
Blocking fractalkine (CX3CL1) in liver ischemia-reperfusion (I/R) mildly reduced platelet and leukocyte adhesion. However, it did not significantly improve overall liver injury or perfusion failure.
Area of Science:
- Immunology
- Hepatology
- Cardiovascular Research
Background:
- Fractalkine (CX3CL1) plays a key role in inflammatory diseases and ischemia-reperfusion (I/R) injury.
- CX3CL1 involvement in platelet and leukocyte activation during hepatic I/R remains incompletely understood.
Purpose of the Study:
- To investigate the role of CX3CL1 in platelet and leukocyte activation during hepatic I/R in a mouse model.
- To assess the therapeutic potential of blocking CX3CL1 in mitigating liver I/R injury.
Main Methods:
- C57BL6 mice underwent warm hepatic I/R (90 min ischemia/240 min reperfusion).
- Animals were pretreated with a function-blocking anti-CX3CL1 antibody or IgG control.
- Intravital microscopy, transaminase levels, and histopathology evaluated inflammatory response and hepatocellular injury.
Main Results:
- Hepatic I/R significantly increased sinusoidal perfusion failure, leukocyte recruitment, and transaminase levels.
- Anti-CX3CL1 antibody treatment significantly reduced firm adhesion of platelets and leukocytes.
- CX3CL1 inhibition attenuated leukocyte adhesion but did not significantly improve perfusion failure or hepatocellular injury.
Conclusions:
- CX3CL1 blockade had a mild attenuating effect on platelet and leukocyte accumulation in hepatic I/R.
- CX3CL1 inhibition did not significantly improve overall hepatocellular injury or perfusion failure during early reperfusion.
- The study highlights a specific role for CX3CL1 in leukocyte adhesion dynamics within the context of liver I/R.
Introduction:
The chemokine fractalkine (CX3CL1) is critically involved in the pathophysiology of different inflammatory diseases and myocardial ischemia-reperfusion (I/R). This study aimed to analyze the role of CX3CL1 in the activation of platelets and leukocytes during hepatic I/R.
Methods:
Under inhalation anesthesia, C57BL6 mice were subjected to warm hepatic I/R (90 min/240 min). The animals were pretreated either with a function-blocking anti-mouse CX3CL1 antibody or IgG control administered systemically before ischemia. Sham-operated animals served as controls (n = 7 each group). The inflammatory response and sinusoidal perfusion failure were evaluated by intravital microscopy. Hepatic transaminases plasma levels and histopathological tissue damage were determined as markers of hepatocellular injury.
Results:
Sinusoidal perfusion failure, leukocyte recruitment to the liver, and transaminase activities were sharply increased upon I/R compared to sham-operated mice. Firm adhesion of platelets and concordantly leukocytes to endothelial cells is reduced significantly by a function-blocking anti-CX3CL1 antibody. We demonstrate that inhibition of CX3CL1 signaling attenuates leukocyte adhesion in the postischemic liver but does not significantly ameliorate overall perfusion failure and hepatocellular injury.
Discussion/Conclusion:
Our in vivo data demonstrate a mild attenuating effect of CX3CL1 blockade on platelet and leukocyte, but not CD4+ T cell accumulation and activation in hepatic I/R injury. We report a significant effect of blocking chemokine CX3CL1 on sinusoidal perfusion failure without considerably improving overall hepatocellular injury during early reperfusion.
