European Surgical Research

Funken D.a,b,c· Brüggemann A.a,b· Mende K.a,b· Lerchenberger M.a,b· Rentsch M.a,b· Khandoga A.a,b,d

Author affiliations

aDepartment of General, Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital of Munich, Ludwig-Maximilians-University of Munich, Munich, Germany
bWalter-Brendel Centre for Experimental Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany
cDepartment of Pediatric Pulmonology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany
dDepartment of General, Visceral and Vascular Surgery, Main-Kinzig-Clinics, Gelnhausen, Germany

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Article / Publication Details

First-Page Preview

Received: September 28, 2021
Accepted: January 26, 2022
Published online: March 11, 2022

Number of Print Pages: 8
Number of Figures: 4
Number of Tables: 0

ISSN: 0014-312X (Print)
eISSN: 1421-9921 (Online)

For additional information: https://www.karger.com/ESR

Abstract

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.

© 2022 S. Karger AG, Basel

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First-Page Preview

Received: September 28, 2021
Accepted: January 26, 2022
Published online: March 11, 2022

Number of Print Pages: 8
Number of Figures: 4
Number of Tables: 0

ISSN: 0014-312X (Print)
eISSN: 1421-9921 (Online)

For additional information: https://www.karger.com/ESR

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