concanavalin-a and Acute-Lung-Injury

We evaluated concanavalin A (Con A)-induced acute hepatic injury in rats using an empirical mathematical model (EMM) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA).. We allocated 18 rats into 3 groups of six each and intravenously injected them with either 10 mg/kg body weight (BW) of Con A (Con A [10] group), 20 mg/kg BW of Con A (Con A [20] group), or a single dose of of saline (4 mL/kg BW, normal control group). We performed the DCE-MRI studies using Gd-EOB-DTPA (0.025 mmol Gd/kg; 0.1 mL/kg BW) as the contrast agent 24 hours after injection of Con A or saline. We then sampled blood, measured serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and calculated the rate of contrast uptake (α), rate of contrast washout (β), area under the curve (AUC), time to maximum relative enhancement (RE) (T(max)), and elimination half-life of RE (T(1/2)) from the time-signal intensity curves using the EMM.. β values were significantly smaller in the Con A (10) and Con A (20) groups than the control group, but α did not differ significantly among the 3 groups. The AUC value was significantly greater in the Con A (10) group than controls, and the T(max) and T(1/2) values were significantly greater in the Con A (20) group than controls. The β, T(max), and T(1/2) values correlated significantly with AST and ALT.. In conclusion, the EMM is useful for evaluating Con A-induced acute hepatic injury using DCE-MRI with Gd-EOB-DTPA.

Topics: Acute Lung Injury; Animals; Computer Simulation; Concanavalin A; Contrast Media; Disease Models, Animal; Gadolinium DTPA; Humans; Image Enhancement; Magnetic Resonance Imaging; Male; Models, Biological; Rats; Rats, Wistar; Reproducibility of Results; Sensitivity and Specificity

Interleukin (IL)-33, a member of the IL-1 cytokine family, positively correlates with acute hepatitis and chronic liver failure in mice and humans. IL-33 is expressed in hepatocytes and is regulated by natural killer T (NKT) cells during concanavalin A (ConA)-induced acute liver injury. Here, we investigated the molecular mechanisms underlying the expression of IL-33 during acute hepatitis. The expression of IL-33 and its regulation by death receptor pathways was investigated after the induction of ConA-acute hepatitis in wildtype (WT), perforin(-/-) , tumor necrosis factor related apoptosis inducing ligand (TRAIL)(-/-) , and NKT cell-deficient (CD1d(-/-) ) mice. In addition, we used a model of acute liver injury by administering Jo2/Fas-antibody or D-galactosamine-tumor necrosis factor alpha (TNFα) in WT mice. Finally, the effect of TRAIL on IL-33 expression was assessed in primary cultured murine hepatocytes. We show that IL-33 expression in hepatocytes is partially controlled by perforin during acute liver injury, but not by TNFα or Fas ligand (FasL). Interestingly, the expression of IL-33 in hepatocytes is blocked during ConA-acute hepatitis in TRAIL-deficient mice compared to WT mice. In contrast, administration of recombinant murine TRAIL associated with ConA-priming in CD1d-deficient mice or in vitro stimulation of murine hepatocytes by TRAIL but not by TNFα or Jo2 induced IL-33 expression in hepatocytes. The IL-33-deficient mice exhibited more severe ConA liver injury than WT controls, suggesting a protective effect of IL-33 in ConA-hepatitis.. The expression of IL-33 during acute hepatitis is dependent on TRAIL, but not on FasL or TNFα.

Topics: Acute Lung Injury; Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Concanavalin A; Fas Ligand Protein; Galactosamine; Gene Expression; Hepatitis, Animal; Hepatocytes; Interleukin-33; Interleukins; Mice; Natural Killer T-Cells; Perforin; Primary Cell Culture; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II; RNA, Messenger; TNF-Related Apoptosis-Inducing Ligand; Tumor Necrosis Factor-alpha