Involvement of intrasinusoidal hemostasis in the development of concanavalin a-induced hepatic injury in mice

Miyazawa, Yuko; Tsutsui, Hiroko; Mizuhara, Hidekazu; Fujiwara, Hiromi; Kaneda, Kenji

doi:10.1002/hep.510270225

Cited by 61 publications

(82 citation statements)

References 30 publications

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“…20 Con A activates T cells and release TNF-␣ and IFN-␥, both of which are critically involved in the development of hepatitis. [19][20][21][22] Although agglutination activity of Con A also contributes to the development of hepatic injury in cooperation with T-cell activation-provoked cytokine production via the induction of intrasinusoidal hemostasis, 23 lymphocyte adhesion to the vessels is not likely to directly result from this activity because distribution of Con A deposits in the hepatic vasculature did not always coincide with that of lymphocyte adhesion in this study. Consistent with this view, Vicia fabla which exceeds the agglutination properties of Con A does not induce hepatitis probably because of the lack of T-cell activation.…”

Section: Discussionmentioning

confidence: 55%

“…17 In this model, following the attachment to endothelial cells, lymphocytes promptly migrate out of the vessels and accumulate in the perivascular areas such as the space of Disse, perivenular interstitial tissue, and portal tract. 18 Tumor necrosis factor-␣ (TNF-␣) and interferon gamma (IFN-␥) released from activated T cells [19][20][21][22][23] play important roles in the development of this disorder. T-cell cytotoxicity mediated by Fas-Fas ligand 24 or perforin 25 might be also involved in hepatic injury.…”

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confidence: 99%

“…nt, not tested. Data other than those of ConA ϩ ␣VCAM-1 and ConA ϩ ␣E-selectin are cited from Miyazawa et al 23 *P Ͻ .01, †P Ͻ .05 versus Con A ϩ rat IgG.…”

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confidence: 99%

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Sublobular veins as the main site of lymphocyte adhesion/transmigration and adhesion molecule expression in the porto-sinusoidal-hepatic venous system during concanavalin A-induced hepatitis in mice

et al. 2000

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Lymphocyte infiltration is a manifest feature of hepatitis. To reveal the main site and mechanism of lymphocyte adhesion/extravasation in the hepatic vasculature during inflammation, we morphometrically and histologically analyzed these events in relation to adhesion molecule expression using a murine model of T-cell mediated hepatitis induced by concanavalin A (Con A). Although lymphocyte adhesion was restricted to the sinusoids in untreated mice, it increased in all the segments of porto-sinusoidal-hepatic venous system 8 hours after Con A injection; the number of adhering lymphocytes per unit vascular circumference was the largest in the sublobular veins, relatively large in the central veins and small hepatic veins, and relatively small in the sinusoids and negligible in the portal veins. At 20 hours, extravascular lymphocytes showed similar distribution to lymphocyte adhesion at 8 hours except in the portal veins, around which they were possibly accumulated by the translocation of extrasinusoidal lymphocytes. E-selectin and vascular cell adhesion molecule-1 (VCAM-1) were transiently expressed at 4 to 6 hours, whereas P-selectin and intercellular adhesion molecule-1 were not changed between 0 and 48 hours. In particular, E-selectin expression coincided with that of lymphocyte adhesion in distribution.

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Section: Discussionmentioning

confidence: 55%

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confidence: 99%

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Sublobular veins as the main site of lymphocyte adhesion/transmigration and adhesion molecule expression in the porto-sinusoidal-hepatic venous system during concanavalin A-induced hepatitis in mice

et al. 2000

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“…7 It is characterized by massive hepatocellular degeneration and lymphoid infiltration in the liver. 8 The hepatitis induced by Con A is dependent on T-cell activation, as indicated by nonoccurrence in athymic nude mice, SCID mice, and FK506-pretreated mice. 9,10 Tissue injury caused by Con A administration is limited to the liver.…”

Section: Eflunomide [Hwa-486; N-(4-trifluoromethyl-mentioning

confidence: 99%

Leflunomide protects from T-cell-mediated liver injury in mice through inhibition of nuclear factor κB

et al. 2004

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Leflunomide is a novel immunosuppressive and anti-inflammatory agent for the treatment of autoimmune disease. The aim of this study was to investigate whether leflunomide protects from liver injury induced by concanavalin A (Con A), a T-cell-dependent model of liver damage. BALB/c mice were injected with 25 mg/kg Con A in the presence or absence of 30 mg/kg leflunomide. Liver injury was assessed biochemically and histologically. Levels of circulating cytokines and expressions of cytokine messenger RNA (mRNA) in the liver and the spleen were determined. Treatment with leflunomide markedly reduced serum transaminase activities and the numbers of dead liver cells. Leflunomide significantly inhibited increases in plasma tumor necrosis factor alpha (TNF-␣) and interleukin 2 concentrations, and also reduced TNF-␣ mRNA expression in the liver after administration of Con A. These findings were supported by the results in which leflunomide administration decreased the number of T lymphocytes infiltrating the liver as well as inhibiting their production of TNF-␣. Activation of nuclear factor B (NF-B), which regulates TNF-␣ production, was inhibited in the liver of mice treated with leflunomide, resulting in a reduction of TNF-␣ production from lymphocytes infiltrating the liver. In conclusion, leflunomide is capable of regulating T-cell-mediated liver injury in vivo and that this event may depend on the decrease of TNF-␣ production in the liver through inhibition of NF-B activation caused by leflunomide.

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“…ConA-induced hepatic injury in mice has long been established as a model of immunologically induced hepatocyte injury because its histological features highly resemble those of viral or druginduced acute hepatitis in humans [18] . The hepatocyte injury is associated with massive hepatocellular degeneration and lymphoid infiltration of the liver [19] . The hepatic injury induced by ConA depends mainly upon T-cell activation [20] , which raises the plasma levels of various cytokines such as tumor necrosis factor-alpha (TNF-α), interferon (IFN)-γ, interleukin (IL)-6, etc [21] .…”

Section: Involvement Of Rest Corepressor 3 In Prognosis Of Human Hepamentioning

confidence: 99%

Involvement of REST corepressor 3 in prognosis of human hepatitis B

Xue

Zheng

et al. 2011

Acta Pharmacol Sin

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Aim: To examine the potential correlation between serum REST corepressor 3 (RCOR3) level and the outcome of patients with hepatitis B. Methods: Concanavalin A (ConA)-induced mouse hepatitis model was used. The mRNA level of RCOR3 in mouse liver was measured using GeneChip array and real-time PCR. One hundred seventy-seven patients with hepatitis B and 34 healthy individuals were categorized into six groups including mild chronic hepatitis, moderate chronic hepatitis B, severe hepatitis B (SHB), cirrhosis, hepatocellular carcinoma (HCC) and healthy control. Serum levels of human RCOR3 were measured using ELISA. Results: In the mouse hepatitis model, the mRNA level of RCOR3 in liver was reduced early after exposure to ConA, then increased after 6 h of exposure. There was no significant difference in the serum RCOR3 level between the mild chronic hepatitis B and the control groups. The serum RCOR3 level was significantly increased in the moderate chronic hepatitis B group, but significantly reduced in SHB, cirrhosis and HCC groups, as compared with the control group. Moreover, the serum RCOR3 levels in SHB, cirrhosis and liver cancer patients were significantly lower than those in the patients with moderate chronic hepatitis B and with mild chronic hepatitis B. Rank correlation analysis revealed a significant correlation between serum RCOR3 level and total bilirubin (r=-0.305, P<0.01). There was no significant correlation between RCOR3 on one hand, and alanine transaminase (r=0.014, P>0.05) or aspartate transaminase (r=-0.079, P>0.05) on the other hand. Conclusion: Serum RCOR3 level may reflect the degree of liver damage, which might be a potential biomarker for the outcome of patients with hepatitis B.

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Involvement of intrasinusoidal hemostasis in the development of concanavalin a-induced hepatic injury in mice

Cited by 61 publications

References 30 publications

Sublobular veins as the main site of lymphocyte adhesion/transmigration and adhesion molecule expression in the porto-sinusoidal-hepatic venous system during concanavalin A-induced hepatitis in mice

Sublobular veins as the main site of lymphocyte adhesion/transmigration and adhesion molecule expression in the porto-sinusoidal-hepatic venous system during concanavalin A-induced hepatitis in mice

Leflunomide protects from T-cell-mediated liver injury in mice through inhibition of nuclear factor κB

Involvement of REST corepressor 3 in prognosis of human hepatitis B

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