L-Tryptophan-Kynurenine Pathway Metabolite 3-Hydroxyanthranilic Acid Induces Apoptosis in Macrophage-Derived Cells Under Pathophysiological Conditions

  • Toshiko Morita
  • Kuniaki Saito
  • Masao Takemura
  • Naoya Maekawa
  • Suwako Fujigaki
  • Hidehiko Fujii
  • Hisayasu Wada
  • Shoji Takeuchi
  • Akio Noma
  • Mitsuru Seishima
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 467)

Abstract

Accumulation of L-kynurenine and 3-hydroxyanthranilic acid (3HAA) occurs in the monocyte-derived cells following immune stimulation, and may derive from L-tryptophan following induction of indoleamine-2,3-dioxygenase. In the present study, we evaluate the possibility that 3HAA acts as an endogenous inducer of monocyte/macrophage apoptosis. Supplementation with 200 μM of 3HAA, but not other L-tryptophan metabolites tested, significantly increased the number of apoptotic cells in both THP-1 and U937 cells. Catalase, superoxide dismutase and manganese ions markedly enhanced apoptosis in the presence of 3HAA in these cells. The present results suggest that 3HAA induces the macrophage/monocyte apoptosis under certain conditions, which may be relevant to patho-physiology of inflammatory conditions.

Keywords

Leukemia Serotonin Pyruvate Tryptophan Melatonin 

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References

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Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Toshiko Morita
    • 1
  • Kuniaki Saito
    • 1
  • Masao Takemura
    • 1
  • Naoya Maekawa
    • 1
  • Suwako Fujigaki
    • 1
  • Hidehiko Fujii
    • 1
  • Hisayasu Wada
    • 1
  • Shoji Takeuchi
    • 1
  • Akio Noma
    • 1
  • Mitsuru Seishima
    • 1
  1. 1.Department of Laboratory MedicineGifu University School of MedicineGifuJapan

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