HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Published online before print February 3, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: jlb.0905527v1 79/4/696    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kawasuji, A. Articles by Sato, S. Search for Related Content PubMed PubMed Citation Articles by Kawasuji, A. Articles by Sato, S.

(Journal of Leukocyte Biology. 2006;79:696-705.)
© 2006 by Society for Leukocyte Biology

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

Ayako Kawasuji^*, Minoru Hasegawa^*,1, Mayuka Horikawa^*, Tomoyuki Fujita^*, Yukiyo Matsushita^*, Takashi Matsushita^*, Manabu Fujimoto^*, Douglas A. Steeber, Thomas F. Tedder, Kazuhiko Takehara^* and Shinichi Sato

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

¹Correspondence: Department of Dermatology, Kanazawa University Graduate School of Medical Science, 13-1, Takara-machi, Kanazawa, 920-8641, Japan. E-mail: minoruha{at}derma.m.kanazawa-u.ac.jp

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-, and ICAM-1 deficiency reduced expression of interleukin-4. By contrast, reductions in liver macrophage inhibitor protein-1 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

This article has been cited by other articles:

				P. F. LALOR, C. TUNCER, C. WESTON, A. MARTIN-SANTOS, D. J. SMITH, and D. H. ADAMS Vascular Adhesion Protein-1 as a Potential Therapeutic Target in Liver Disease Ann. N.Y. Acad. Sci., September 1, 2007; 1110(1): 485 - 496. [Abstract] [Full Text] [PDF]