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Production of leukotriene B4 in parenchymal and sinusoidal cells of the liver in rats treated simultaneously with D-galactosamine and endotoxin

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Summary

A study was conducted to investigate production rate of leukotriene B4 (LTB4) in parenchymal and sinusoidal liver cells of rats with acute hepatic failure (AHF). AHF was induced by simultaneous administration of D-galactosamine (GalN) and endotoxin (LPS), and parenchymal as well as sinusoidal liver cells were isolated by collagenase perfusion method. Following preincubation for 15 min, isolated cellular fractions were incubated with Ca-ionophore (2µM) for 5 min, and levels of LTB4 in culture media before and 5 min after addition of Ca-ionophore were analyzed by HPLC. Following results were obtained: The production rate of LTB4 was found to be the highest in Kupffer cells (7.2ng/106 cells/5 min), followed by endothelial cells (1.1), stellate cells (0.2) and parenchymal cells (not detectable). The production rate of LTB4 in both Kupffer cells and endothelial cells was found to reach a maximum in the fraction isolated 60 min after administration of GalN and LPS. Treatment with AA861, one of the selective inhibitors of 5-lipoxygenase, was shown to reduce the production of LTB4 in Kupffer cells to 53% at 10-7M and above 99% at higher than 10-5M. In conclusion, the majority of LTB4 generated in the liver of rats with AHF was found to be synthesized in Kupffer cells and, to a lesser extent, in endothelial cells, and the enhanced production of LTB4 was found to be greatly inhibited by treatment with AA861.

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Authors and Affiliations

  1. First Department of Internal Medicine, Gifu University School of Medicine, 40 Tsukasa-machi, 500, Gifu City, Japan

    Yoshimune Shiratori, Hisataka Moriwaki, Yasutoshi Muto M.D. (Professor and Chairman), Hiroo Onishi, Michimasa Kato & Fumihiro Asano

Authors
  1. Yoshimune Shiratori
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  2. Hisataka Moriwaki
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  3. Yasutoshi Muto M.D.
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  4. Hiroo Onishi
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  5. Michimasa Kato
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  6. Fumihiro Asano
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Additional information

This work was supported in part by a Grant-in-Aid from the Ministry of Health and Welfare, and by a 1987 Award from Tokai Academic Research Grant to HM.

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Shiratori, Y., Moriwaki, H., Muto, Y. et al. Production of leukotriene B4 in parenchymal and sinusoidal cells of the liver in rats treated simultaneously with D-galactosamine and endotoxin. Gastroenterol Jpn 24, 640–645 (1989). https://doi.org/10.1007/BF02774162

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  • DOI: https://doi.org/10.1007/BF02774162

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