Suppression of hepatic lymphokine-activated killer cell induction by murine Kupffer cells and hepatocytes

Shie Pon Tzung, Katherine C. Gaines, Michael P Lance, M. Jane Ehrke, Stefan A. Cohen

Research output: Contribution to journalArticle

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Abstract

Murine lymphokine-activated-killer cell activity was readily induced by culturing spleen cells with 10 U/ml of interleukin-2 for 4 days. In contrast, very little activity was generated under the same culture conditions when nonparenchymal liver cells were used as the responding cells. It was concluded that Kupffer cells produced prostaglandin and interferon α/β, which suppressed lymphokine-activated-killer induction because (a) induction of lymphokine-activated-killer activity from nonparenchymal liver cells was observed in the presence of indomethacin and anti-interferon á/â antibody; (b) when adherent nonparenchymal liver cells, primarily Kupffer cells, were removed, lymphokine-activated-killer activity could be obtained with interleukin-2 alone; (c) coculture of Kupffer cells with nonadherent nonparenchymal liver cells in a two-chambered system inhibited lymphokine-activated killer cell induction in a dose-dependent manner; (d) exogenous prostaglandin E2 and interferon α/β added at the start of culture inhibited interleukin-2-induced cytotoxicity and proliferation, whereas the other major prostaglandin species in the liver, prostaglandin D2, had little effect. These findings are distinctive with Kupffer cells because splenic macrophages did not exert such inhibition in parallel experiments. Moreover, the supernatant collected from the 24-hr culture of nonparenchymal liver cells contained greater than 20-fold more prostaglandin E2 and interferon α/β than that from culture of spleen cells. In subsequent ire vivo experiments, when interleukin-2 was given intraperitoneally to mice, the combination of indomethacin and anti-interferon α/β antibody significantly enhanced lymphokine-activated-killer activity recovered from the liver. Besides Kupffer cells, it was found that hepatocytes, the major cellular component of the liver, also played an inhibitory role on lymphokine-activated-killer cell generation. A cell-free liver cytosolic extract had even more potent suppressive effect, which was partially reversed by supplementation of arginine, indicating that arginase may be one of the hepatocyte-derived immunoinhibitors.

Original languageEnglish (US)
Pages (from-to)644-652
Number of pages9
JournalHepatology
Volume12
Issue number4
StatePublished - Oct 1990
Externally publishedYes

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Lymphokine-Activated Killer Cells
Kupffer Cells
Hepatocytes
Interferons
Lymphokines
Liver
Interleukin-2
Dinoprostone
Indomethacin
Prostaglandins
Anti-Idiotypic Antibodies
Spleen
Prostaglandin D2
Arginase
Liver Extracts
Coculture Techniques
Interleukin-4
Arginine
Cell Culture Techniques
Macrophages

ASJC Scopus subject areas

  • Hepatology

Cite this

Tzung, S. P., Gaines, K. C., Lance, M. P., Ehrke, M. J., & Cohen, S. A. (1990). Suppression of hepatic lymphokine-activated killer cell induction by murine Kupffer cells and hepatocytes. Hepatology, 12(4), 644-652.

Suppression of hepatic lymphokine-activated killer cell induction by murine Kupffer cells and hepatocytes. / Tzung, Shie Pon; Gaines, Katherine C.; Lance, Michael P; Ehrke, M. Jane; Cohen, Stefan A.

In: Hepatology, Vol. 12, No. 4, 10.1990, p. 644-652.

Research output: Contribution to journalArticle

Tzung, SP, Gaines, KC, Lance, MP, Ehrke, MJ & Cohen, SA 1990, 'Suppression of hepatic lymphokine-activated killer cell induction by murine Kupffer cells and hepatocytes', Hepatology, vol. 12, no. 4, pp. 644-652.
Tzung, Shie Pon ; Gaines, Katherine C. ; Lance, Michael P ; Ehrke, M. Jane ; Cohen, Stefan A. / Suppression of hepatic lymphokine-activated killer cell induction by murine Kupffer cells and hepatocytes. In: Hepatology. 1990 ; Vol. 12, No. 4. pp. 644-652.
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abstract = "Murine lymphokine-activated-killer cell activity was readily induced by culturing spleen cells with 10 U/ml of interleukin-2 for 4 days. In contrast, very little activity was generated under the same culture conditions when nonparenchymal liver cells were used as the responding cells. It was concluded that Kupffer cells produced prostaglandin and interferon α/β, which suppressed lymphokine-activated-killer induction because (a) induction of lymphokine-activated-killer activity from nonparenchymal liver cells was observed in the presence of indomethacin and anti-interferon {\'a}/{\^a} antibody; (b) when adherent nonparenchymal liver cells, primarily Kupffer cells, were removed, lymphokine-activated-killer activity could be obtained with interleukin-2 alone; (c) coculture of Kupffer cells with nonadherent nonparenchymal liver cells in a two-chambered system inhibited lymphokine-activated killer cell induction in a dose-dependent manner; (d) exogenous prostaglandin E2 and interferon α/β added at the start of culture inhibited interleukin-2-induced cytotoxicity and proliferation, whereas the other major prostaglandin species in the liver, prostaglandin D2, had little effect. These findings are distinctive with Kupffer cells because splenic macrophages did not exert such inhibition in parallel experiments. Moreover, the supernatant collected from the 24-hr culture of nonparenchymal liver cells contained greater than 20-fold more prostaglandin E2 and interferon α/β than that from culture of spleen cells. In subsequent ire vivo experiments, when interleukin-2 was given intraperitoneally to mice, the combination of indomethacin and anti-interferon α/β antibody significantly enhanced lymphokine-activated-killer activity recovered from the liver. Besides Kupffer cells, it was found that hepatocytes, the major cellular component of the liver, also played an inhibitory role on lymphokine-activated-killer cell generation. A cell-free liver cytosolic extract had even more potent suppressive effect, which was partially reversed by supplementation of arginine, indicating that arginase may be one of the hepatocyte-derived immunoinhibitors.",
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