Pepro Tech
A more recent version of this article appeared on April 1, 2006

Published online before print February 3, 2006
This Article
Right arrow Full Text (Reprint (PDF))
Right arrow All Versions of this Article:
jlb.0905527v1
79/4/696    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kawasuji, A.
Right arrow Articles by Sato, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kawasuji, A.
Right arrow Articles by Sato, S.
© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0905527

Received for publication September 19, 2005.
Revised November 6, 2005.
Accepted for publication November 29, 2005.

Article

L-selectin and intercellular adhesion molecule-1 regulate the development of concanavalin A-induced liver injury

Ayako Kawasuji *, Minoru Hasegawa *@, Mayuka Horikawa *, Tomoyuki Fujita *, Yukiyo Matsushita *, Takashi Matsushita *, Manabu Fujimoto *, Douglas A. Steeber {dagger}, Thomas F. Tedder {ddagger}, Kazuhiko Takehara *, and Shinichi Sato {sect}

*Department of Dermatology, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan; {dagger}Department of Biological Sciences, University of Wisconsin-Milwaukee; {ddagger}Department of Immunology, Duke University Medical Center, Durham, North Carolina; and {sect}Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, Japan

@ To whom correspondence should be addressed. E-mail: minoruha{at}derma.m.kanazawa-u.ac.jp.


arrow
Abstract

Concanavalin A (Con A)-induced hepatitis is a model for human T cell-mediated hepatitis. We evaluated the role of L-selectin and intercellular adhesion molecule-1 (ICAM-1) in this model by injecting Con A intravenously in mice lacking L-selectin (L-selectin-/-), ICAM-1 (ICAM-1-/-), or both (L-selectin/ICAM-1-/-). Blood and liver samples were collected 0, 8, 24, and 48 h after Con A treatment. Increases in plasma transaminase levels, which peaked 8 h after injection, were reduced significantly in L-selectin-/-, ICAM-1-/-, and L- selectin/ICAM-1-/- mice compared with wild-type mice. Liver necrosis was more strongly inhibited in ICAM-1-/- mice than in L-selectin-/- mice but was most prominently reduced in L-selectin/ ICAM-1-/- mice, in parallel with decreased plasma transaminase levels. The reduced severity of hepatitis in the mutant mice correlated with decreases in numbers of liver CD4+ T cells but not numbers of CD8+ T cells or neutrophils. Following Con A treatment, L-selectin deficiency reduced liver mRNA expression of tumor necrosis factor-{alpha}, and ICAM-1 deficiency reduced expression of interleukin-4. By contrast, reductions in liver macrophage inhibitor protein-1{alpha} mRNA occurred in all mutant mice. These results indicate that L-selectin and ICAM-1 contribute cooperatively to the development of Con A-induced hepatitis by regulating leukocyte infiltration and subsequent cytokine production.

Key Words: hepatitis • cytokine • animal model