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1987 Fiscal Year Final Research Report Summary

Mechanisms of Fusion of Macrophages Induced by 1 ,25(OH)_2D_3

Research Project

Project/Area Number 60440086
Research Category

Grant-in-Aid for General Scientific Research (A)

Allocation TypeSingle-year Grants
Research Field Functional basic dentistry
Research InstitutionShowa University

Principal Investigator

SUDA Tatsuo  School of Dentistry, Showa University, 歯学部, 教授 (90014034)

Co-Investigator(Kenkyū-buntansha) TANAKA Hirofumi  School of Dentistry, Showa University, 歯学部, 助手 (30146899)
MIYAURA Chisato  School of Dentistry, Showa University, 歯学部, 助手 (20138382)
TAKAHASHI Naoyuki  School of Dentistry, Showa University, 歯学部, 講師 (90119222)
SHINKI Toshimasa  School of Dentistry, Showa University, 歯学部, 講師 (90138420)
ABE Etsuko  School of Dentistry, Showa University, 歯学部, 助教授 (70119147)
Project Period (FY) 1985 – 1987
KeywordsVitamin D / Macrophages / Cell-fusion / Osteoclast / 分化誘導因子
Research Abstract

We have reported that 1<alpha>,25-dihydroxyvitamin D_3 [1<alpha>,25(OH)_2D_3] directly induces fusion of mouse alveolar macrophages at a very high rate (circa 70-80%) by a mechanism involving protein synthesis (Proc. Natl. Acad. Sci. USA 80:5583,1983; FEBS Letters 174:61,1984). While examining further the mechanism of the 1<alpha>,25(OH)_2D_3-induced fusion of macrophages, we found that polyamines are involved in this mechanism. Mouse alveolar macrophages incubated with 12 nM 1<alpha>,25(OH)_2D_3 began to fuse at 36 h and the fusion rate increased linearly up to 60 h. Addition of as much as 0.05 - 5 mM -difluoromethylornithine (<alpha>-DFMO), a specific inhibitor of ornithine decarboxylase, did not inhibit fusion appreciably, but addition of 0.05 - 5<mu>M methylglyoxal bis (guanylhydrazone) (MGBG), an inhibitor of S-adenosylmethionine decarboxylase, strikingly inhibited fusion. When macrophages were treated with both 12 nM 1<alpha>,25(OH)_2D2_3 and 5 <mu>M MGBG for the first 12 h and i … More ncubated further for 60 h in fresh medium containing 1<alpha>,25(OH)_2D_3, fusion was significantly inhibited, suggesting that the 1<alpha>,25(OH)_2D_3-induced synthesis of polyamines precedes fusion. The inhibition by MGBG of the 1<alpha>,25(OH)_2D_3-induced fusion was restored completely by adding 1 <mu>M spermidine or spermine or 100 M putrescine. None of the polyamines alone induced fusion. MGBG suppressed the 1<alpha>,25(OH)_2D_3-induced incorporation of [^3H]-leucine into the trichloroacetic acid-insoluble fraction in macrophages, but its inhibitory effect was restored completely by adding 1<mu> M spermidine. When macrophages were incubated with [^<14>C]-ornithine, the polyamine that accumulated most was [^<14>C]-spermidine. 1<alpha>,25(OH)_2D_3 further enhanced the accumulation of [^<14>C] putrescine and spermine was not appreciably altered by the 1<alpha>,25(OH)_2D_3 treatment. Adding MGBG almost completely suppressed the accumulation of [^<14>C]-spermidine and spermine, but it enhanced the accumulation of [^<14>C]-putrescine considerably. These results indicate that spermidine or spermine is an important intracellular mediator of the 1<alpha>,25(OH)_2D_3 action in inducing protein synthesis, which in turn somehow induces fusion of alvolar macrophages. Less

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Takamune Hayashi: J.Bore Miner, Res.1. 235-242 (1986)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshiko Shiina: Calcif. Tissue Int.39. 28-34 (1986)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chisato Miyaura: J. Bone Miner. Res.1. 359-368 (1986)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Etsuko Abe: Proc. Natl. Acad. Sci. USA. 83. 5958-5962 (1986)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chisato Miyaura: Endocrinology. 120. 1813-1820 (1987)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Etsuko Abe: Endocrinology. 121. 271-277 (1987)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tatsuo Suda: "Bone and Mineral Research No4" ELSVIER(Amsterdam-New York-Oxford), 1-48 (1986)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 須田 立雄: "Super Illustrations:カルシウム代謝と活性型ビタミンD" 協和企画(東京), 1-83 (1986)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takamune Hayashi: "Polyamines are involved in the 1<alpha>,25-dihydroxyvitamin D_3-induced fusion of mouse alveolar macrophages." J. Bone Miner. Res.1. 235-242 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Chisato Miyaura: "Effects of retinoic acid on the activation and fusion of mouse alveolar macrophages induced by 1<alpha>,25-dihydroxyvitamin D_3." J. Bone Miner. Res.1. 359-368 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Etsuko Abe: "Differentiation-inducing factor purified from conditioned medium of mitogen-treated spleen cell cultures stimulates bone resorption." Proc. Natl. Acad. Sci. USA. 83. 5958-5962 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Chisato Miyaura: "Alteration of lipid metabolism associated with the activation of mouse alveolar macrophages induced by 1<alpha>,25-dihydroxyvitamin D_3." Endocrinology. 120. 1813-1820 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Etsuko Abe: "The relationship between fusion and proliferation in mouse alveolar macrophages." Endocrinology. 121. 271-277 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tatsuo Suda: Bone and Mineral Research No.4. ELSEVIER, 1-48 (1986)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1989-03-30  

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