Blockage of CX3CL1 Attenuates Platelet and Leukocyte Recruitment in Murine Hepatic I/R
| Autor: | Dominik Funken, Alexandra Brüggemann, Konstantin Mende, Maximilian Lerchenberger, Markus Rentsch, Andrej Khandoga |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | European Surgical Research. :1-8 |
| ISSN: | 1421-9921 0014-312X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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