metallothionein and Shock--Septic

Two different metallothionein promoter-mouse CD14 fusion genes were constructed. The membrane form of the CD14 fusion gene, designated M14M, contained the full-length CD14 cDNA sequence, whereas the soluble form of the fusion gene, designated M14S, was truncated to lack the sequence for the phosphatidylinositol-anchoring site. Expression of transgenic RNA in M14M and M14S mice on the basal diet was abundant in the liver. After maintenance with water containing ZnSO4 (50 mM) for 4 days, expression of transgenic RNA in M14M and M14S mice was strong in the small intestine. Immunohistochemical analysis demonstrated CD14 expression in these organs in M14S and M14M mice. Levels of CD14 in sera from M14S mice after zinc administration were significantly higher than these animals maintained with normal water, M14M mice after zinc administration and non-transgenic mice. Sera from M14S and M14M mice after stimulation with lipopolysaccharide LPS (LPS) demonstrated significantly lower levels of tumor necrosis factor-alpha and IL-6 than those from non-transgenic mice. Lethality in endotoxin shock produced by i.p. injection of 30-40 microg/g body wt LPS was not different between M14S, M14M and non-transgenic mice. However, survival rates in the lethal Shwartzman reaction induced by priming and challenge injections of LPS were significantly higher in M14M and M14S mice than in non-transgenic mice.

Topics: Animals; Crosses, Genetic; Cytokines; Female; Heterozygote; Interleukin-6; Intestine, Small; Lipopolysaccharide Receptors; Lipopolysaccharides; Liver; Male; Metallothionein; Mice; Mice, Inbred C57BL; Mice, Transgenic; Recombinant Fusion Proteins; RNA, Messenger; Shock, Septic; Solubility; Tumor Necrosis Factor-alpha

Zinc metabolism in endotoxicosis was investigated in rats. The zinc concentration in the serum decreased, while zinc contents increased in the lung, kidney and liver. Marked increase in zinc level was observed in the liver. In the liver cells, zinc concentrations of mitochondria and cytosol increased, but not in microsome. Metallothioneins (MTs), which probably participate in zinc metabolism, were induced by endotoxin administration. Although the same level of MT-2 as that of MT-1 was induced by zinc, the level of MT-2 was 3 to 4 fold higher than that of MT-1 by administrations of endotoxin or glucocorticoid hormone. Since no metallothionein was induced directly by addition of endotoxin to the media of cultured cells, the endotoxin was found not to induce MTs directly. The effect of zinc on superoxide generation of polymorphonuclear leukocytes was also studied. Zinc was found to inhibit superoxide generation dose-dependently.

Topics: Animals; Cell Line; Endotoxins; Humans; Kidney; Kinetics; Liver; Lung; Metallothionein; Neutrophils; Rats; Serum Albumin, Bovine; Shock, Septic; Superoxides; Tetradecanoylphorbol Acetate; Zinc

Topics: Animals; Cadmium; Chemical Phenomena; Chemistry; Horses; Humans; Kidney; Liver; Metallothionein; Metals; Protein Binding; Rabbits; Shock, Septic; Species Specificity