| First Author | Kawasuji A | Year | 2006 |
| Journal | J Leukoc Biol | Volume | 79 |
| Issue | 4 | Pages | 696-705 |
| PubMed ID | 16461740 | Mgi Jnum | J:107551 |
| Mgi Id | MGI:3621403 | Doi | 10.1189/jlb.0905527 |
| Citation | Kawasuji A, et al. (2006) L-selectin and intercellular adhesion molecule-1 regulate the development of Concanavalin A-induced liver injury. J Leukoc Biol 79(4):696-705 |
| abstractText | 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. |
