Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Journal of leukocyte biology, 2006-04, Vol.79 (4), p.696-705

Ort / Verlag

United States: Society for Leukocyte Biology

Erscheinungsjahr

2006

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

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