Search PubMed⌕ Search

Biomedical subjects

Y Mizoguchi

Publications and source records attributed to Y Mizoguchi.

At least 235 records · Page 13Linked to original sources

Induction of liver cell injury by antibody-dependent monocyte-mediated cytotoxicity in vitro.

The isolated liver cells coated with the anti-liver cell membrane antibody were damaged by incubation with the peripheral blood mononuclear cells. This was demonstrated by measuring the reduction of protein synthesis in the target liver cells. Adherent cells from the peripheral blood mononuclear cells were shown to have a sufficient capacity acting on the isolated liver cells as an effector when they were separated from the peripheral blood of normal and patients with acute or chronic active hepatitis. However, those from patients with liver cirrhosis or hepatoma did not show such effector activity in antibody-dependent cell-mediated liver cell damage. These results suggest that possibly antibody-dependent macrophage-mediated cytotoxicity may play some role in the induction of liver cell injury because the anti-hepatocyte membrane antibody is frequently detected in patient's sera, especially in those with chronic active hepatitis.

Animals↗

Studies on the mechanism of liver injury by macrophage-mediated cytotoxicity--partial purification of cytotoxic factor detected in the culture supernatant of activated macrophages.

The culture supernatant of activated lymphocytes was shown to contain macrophage activating factor (MAF), a kind of lymphokine, which activated the peritoneal macrophages prepared from guinea pigs. When the culture fluid of the MAF-activated macrophages was added to the isolated liver cells, a significant inhibition of their albumin biosynthesis was demonstrated. The active material was recovered in a definitive fraction by gel filtration using a Sephadex G-75 column and this was further fractionated into two fractions by DEAE-cellulose column chromatography, suggesting that at least two kinds of active substances existed. By isoelectric focusing electrophoresis it was shown that these two active principles were substances having different isoelectric points, by isoelectric focusing electrophoresis. These results suggest that some cytotoxic or cytostatic materials are produced from the lymphokine-activated macrophages and they may participate in the occurrence of liver injury at least partially.

Albumins↗

Lipid peroxide formation in isolated hepatocytes by cytotoxic factors produced from lymphokine-activated macrophages.

When peripheral blood lymphocytes from patients with chronic active hepatitis were stimulated with liver specific lipoprotein (LSP), considerably higher frequencies of lymphocyte transformation and MIF production were induced. Peritoneal macrophages from guinea pigs were activated by lymphokine-containing lymphocyte culture supernatant and produced a cytotoxic (or cytostatic) factor acting on isolated hepatocytes in culture. The cytotoxic (or cytostatic) factor, which was fractionated by Sephadex G-75 column gel filtration followed by DEAE-cellulose column chromatography, had cytotoxic effect on isolated liver cells and produced a significant amount of lipid peroxide. These results suggested the possibility that the cytotoxic effects may be caused at least partially by the lipid peroxide formation.

Cytotoxicity, Immunologic↗

Modulation of cholestatic factor production by serum components.

When lymph node cells from sensitized guinea pigs were stimulated in vitro with a specific antigen and their culture supernatant was injected into the mesenteric vein of rats, a marked decrease in bile flow was demonstrated. The treatment of activated lymphocytes with a higher molecular weight fraction of normal human serum Fr-1 and Fr-2 was shown to decrease the reduction of bile flow. Conversely, a lower molecular weight fraction of serum (Fr-3) was found to augment the reduction of bile flow. These findings suggest that the serum components may regulate the production of a factor (or factors) causing the decrease in bile flow from the activated lymphocytes.

Animals↗

Modulation of the macrophage hepatocytotoxicity and plasminogen activator activity of activated macrophages from guinea pigs by serum components from normal human and patients with liver diseases.

Activated macrophages (m phi) exhibited cytotoxic effects on isolated liver cells and produced plasminogen activator (PA) in vitro. A high molecular weight fraction of normal human serum (Fr-1) was shown to reduce the m phi-mediated hepatocytotoxicity and enhance the PA activity of activated m phi. Conversely, a lower molecular weight fraction of serum (Fr-3) was found to enhance the hepatotoxic potential and decrease the PA activity of activated m phi. Although similar effects were seen with serum fraction prepared from patients with acute hepatitis, somewhat different influences were observed with serum components from patients with chronic active hepatitis or liver cirrhosis: Fr-1 from patients with chronic active hepatitis was less active in reducing m phi-mediated hepatocytotoxicity, and and Fr-3 was more active in enhancing it, in comparison with fractions from individuals or patients with active hepatitis. Fr-3 from patients with liver cirrhosis was shown to be remarkably less active in enhancing m phi-mediated hepatocytotoxicity. Furthermore, Fr-1 from patients with liver cirrhosis reduced PA activity, Fr-3 was less active in decreasing such activity. These findings suggest that the serum components may regulate m phi-mediated hepatocytotoxicity as well as PA secretion of activated m phi. Our studies also suggested the possibility that relative doses of these serum components may differ in various pathological conditions of the liver.

Animals↗