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

Klintman, Daniel LU ; Schramm, René; Menger, Michael D and Thorlacius, Henrik LU (2002) In Journal of Hepatology 36(1). p.53-59
Abstract
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.... (More)
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. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
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
in
Journal of Hepatology
volume
36
issue
1
pages
53 - 59
publisher
Elsevier
external identifiers
  • wos:000173730700009
  • pmid:11804664
  • scopus:0036130188
ISSN
0168-8278
DOI
10.1016/S0168-8278(01)00226-4
language
English
LU publication?
yes
id
fed7236f-eeb9-4508-8fb4-78456510f7a8 (old id 106525)
alternative location
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11804664&dopt=Abstract
date added to LUP
2007-07-24 15:56:05
date last changed
2017-09-24 03:39:34
@article{fed7236f-eeb9-4508-8fb4-78456510f7a8,
  abstract     = {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.},
  author       = {Klintman, Daniel and Schramm, René and Menger, Michael D and Thorlacius, Henrik},
  issn         = {0168-8278},
  keyword      = {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},
  language     = {eng},
  number       = {1},
  pages        = {53--59},
  publisher    = {Elsevier},
  series       = {Journal of Hepatology},
  title        = {Leukocyte recruitment in hepatic injury: selectin-mediated leukocyte rolling is a prerequisite for CD18-dependent firm adhesion.},
  url          = {http://dx.doi.org/10.1016/S0168-8278(01)00226-4},
  volume       = {36},
  year         = {2002},
}