The soluble Notch ligand, Jagged-1, inhibits proliferation of CD34+ macrophage progenitors.
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-l 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.
Masuya
Masahiro
M
Second Department of Internal Medicine, Mie University School of Medicine, Japan.
Katayama
Naoyuki
N
Hoshino
Natsuki
N
Nishikawa
Hiroyoshi
H
Sakano
Seiji
S
Araki
Hiroto
H
Mitani
Hidetsugu
H
Suzuki
Hirohito
H
Miyashita
Hiroyuki
H
Kobayashi
Kyoko
K
Nishii
Kazuhiro
K
Minami
Nobuyuki
N
Shiku
Hiroshi
H
D015703:Antigens, CD / Q000097:blood; D018952:Antigens, CD34 / Q000097:blood; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D016895:Culture Media, Serum-Free; D005312:Fetal Blood / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D007231:Infant, Newborn; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008264:Macrophages / Q000166:cytology*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D011506:Proteins / Q000235:genetics / Q000494:pharmacology*; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000072099:Serrate-Jagged Proteins; D014157:Transcription Factors
D015703:Antigens, CD; D018952:Antigens, CD34; D002135:Calcium-Binding Proteins; D016895:Culture Media, Serum-Free; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; D011506:Proteins; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D000072099:Serrate-Jagged Proteins; D014157:Transcription Factors