Leukocyte recruitment in hepatic injury: selectin-mediated leukocyte rolling is a prerequisite for CD18-dependent firm adhesion.

Daniel Klintman, René Schramm, Michael D Menger, Henrik Thorlacius

Research output: Contribution to journalArticlepeer-review

43 Citations (SciVal)


Background/Aims: This study was designed to examine the role of selectins and CD18 in leukocyte recruitment in hepatic injury induced by tumor necrosis factor-alpha (TNF-alpha) and galactosamine (Gal) in vivo.Methods: Intravital fluorescence microscopy of the hepatic microcirculation was used to quantify leukocyte-endothelium interactions provoked by 24 h of systemic TNF-alpha/Gal challenge in rats. Hepatic injury was evaluated with liver enzymes.Results: When administered after 24 h of TNF-alpha/Gal challenge, fucoidan, a selectin-function inhibitor, reduced leukocyte rolling by 69%, whereas firm adhesion was unaltered. In contrast, passive immunization against CD18 decreased leukocyte adhesion by 60%, whereas rolling remained unchanged. Notably, when administered prior to TNF-alpha/Gal, fucoidan attenuated both leukocyte rolling and adhesion, by 57 and 69%, respectively. Pretreatment with an anti-CD18 antibody decreased TNF-alpha/Gal-induced rolling and firm adhesion by 25 and 90%, respectively. Moreover, pretreatment with fucoidan and the anti-CD18 antibody both protected against TNF-alpha/Gal-induced increases in liver enzymes. For example, the pretreatments reduced alanine aminotransferase by 59 and 87%, respectively.Conclusions: Our data suggest that TNF-alpha/Gal-induced leukocyte rolling is selectin-mediated and a precondition for CD18-dependent firm adhesion in hepatic venules. Thus, reducing leukocyte recruitment by inhibition of selectins or CD18 may be useful to control TNF-alpha-induced liver injury.
Original languageEnglish
Pages (from-to)53-59
JournalJournal of Hepatology
Issue number1
Publication statusPublished - 2002

Bibliographical note

The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Surgery (013242200), Surgery Research Unit (013242220), Emergency medicine/Medicine/Surgery (013240200)

Subject classification (UKÄ)

  • Gastroenterology and Hepatology


  • Liver/blood supply/enzymology/*immunology
  • Leukocytes/cytology
  • Liver Circulation/immunology
  • Male
  • Microscopy
  • Fluorescence
  • Rats
  • Vascular/cytology
  • Endothelium
  • Non-U.S. Gov't
  • Venules/cytology
  • Tumor Necrosis Factor
  • Support
  • Sepsis/chemically induced/*immunology/metabolism
  • Selectins/*metabolism
  • Sprague-Dawley
  • Animal
  • Antigens
  • CD18/*metabolism
  • Antineoplastic Agents
  • Cell Adhesion/physiology
  • Leukocyte/*physiology
  • Chemotaxis
  • Galactosamine


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