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

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-1alpha 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.

• Authors: Ayako Kawasuji, Minoru Hasegawa, Mayuka Horikawa, Tomoyuki Fujita, Yukiyo Matsushita, Takashi Matsushita, Manabu Fujimoto, Douglas A Steeber, Thomas F Tedder, Kazuhiko Takehara, Shinichi Sato
• Journal: Journal of leukocyte biology (J Leukoc Biol) Vol. 79 Issue 4 Pg. 696-705 (Apr 2006) ISSN: 0741-5400 [Print] United States
• PMID: 16461740 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• RNA, Messenger
• Concanavalin A
• Intercellular Adhesion Molecule-1
• L-Selectin
• Transforming Growth Factors

Topics

• Animals
• Chemical and Drug Induced Liver Injury (immunology, metabolism, pathology)
• Concanavalin A (toxicity)
• Cytokines (biosynthesis)
• Disease Models, Animal
• Intercellular Adhesion Molecule-1 (biosynthesis, genetics, immunology)
• L-Selectin (genetics, immunology)
• Leukocytes (drug effects, metabolism)
• Liver (drug effects, immunology, injuries)
• Mice
• Mice, Knockout
• RNA, Messenger (metabolism)
• Time Factors
• Transforming Growth Factors (biosynthesis)