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International Journal of Hematology

, Volume 75, Issue 3, pp 269–276 | Cite as

The Soluble Notch Ligand, Jagged-1, Inhibits Proliferation of CD34+ Macrophage Progenitors

  • Masahiro Masuya
  • Naoyuki Katayama
  • Natsuki Hoshino
  • Hiroyoshi Nishikawa
  • Seiji Sakano
  • Hiroto Araki
  • Hidetsugu Mitani
  • Hirohito Suzuki
  • Hiroyuki Miyashita
  • Kyoko Kobayashi
  • Kazuhiro Nishii
  • Nobuyuki Minami
  • Hiroshi Shiku
Special Report

Abstract

The Notch/Notch ligand system controls diverse cellular processes. The proteolytic cleavage generates transmembrane and soluble forms of Notch ligands.We examined the effect of a soluble Notch ligand, human Jagged-1, on human cord blood (CB) CD34+ cells, under serum-deprived conditions, using soluble human Jagged-1—immunoglobulin G1 chimera protein (hJagged-1). Soluble hJagged-1 inhibited myeloid colony formation but not erythroid-mix or erythroid colony formation, in the presence of stem cell factor (SCF), interleukin-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, thrombopoietin, and erythropoietin. Cytological analysis revealed that the decrease in myeloid colonies resulted mainly from the inhibition of macrophage colony formation. Furthermore, soluble hJagged-1 led to the inhibition of macrophage colony formation supported by M-CSF plus SCF and GM-CSF plus SCF. Delayed-addition experiments and the analysis of colony sizes demonstrated that soluble hJagged-1 inhibited the growth of macrophage progenitors by acting in the early stage of macrophage development. The direct action of hJagged-1 was confirmed by the enhanced expression of the HES-1 (hairy enhancer of the split-1) gene. These results suggest that soluble hJagged-1 may regulate human hematopoiesis in the monocyte/macrophage lineage.

Key Words

CD34+ cells Notch Soluble human Jagged-1 Cord blood CFU-M 

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Copyright information

© The Japanese Society of Hematology 2002

Authors and Affiliations

  • Masahiro Masuya
    • 1
  • Naoyuki Katayama
    • 1
  • Natsuki Hoshino
    • 1
  • Hiroyoshi Nishikawa
    • 1
  • Seiji Sakano
    • 2
  • Hiroto Araki
    • 1
  • Hidetsugu Mitani
    • 1
  • Hirohito Suzuki
    • 1
  • Hiroyuki Miyashita
    • 1
  • Kyoko Kobayashi
    • 1
  • Kazuhiro Nishii
    • 1
  • Nobuyuki Minami
    • 3
  • Hiroshi Shiku
    • 1
  1. 1.Second Department of Internal MedicineMie University School of MedicineMie
  2. 2.The Second Research Department, Central Technology LaboratoryAsahi Kasei CorporationShizuoka
  3. 3.Blood Transfusion ServiceMie University HospitalMieJapan

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