Document Detail

1 alpha,25-Dihydroxyvitamin D3 promotes monocytopoiesis and suppresses granulocytopoiesis in cultures of normal human myeloid blast cells.
MedLine Citation:
PMID:  8071589     Owner:  NLM     Status:  MEDLINE    
Primitive myeloid blast cells (2-10 x 10(6)) were purified from 18-22-week fetal liver-derived mononuclear cell preparations by negative selection followed by counterflow cell elutriation. The cells, when maintained in liquid culture in the presence of 100 U/ml interleukin-3 (IL-3) for the first 5 days and 10 U/ml IL-3 and 30 ng/ml granulocyte colony-stimulating factor thereafter, underwent considerable proliferation resulting in an approximately 30-fold increase in cell number by day 14. Analyses of cell morphology and of the numbers of cells that expressed the neutrophil-associated antigen CD15, the monocyte-associated antigen 61D3, and enzymes alpha-naphthyl acetate esterase (ANAE), human leukocyte elastase, and cathepsin G revealed that proliferation of the cells was associated with their concomitant differentiation toward neutrophils and monocytes. The cultures generated predominantly neutrophils; by day 14, wells seeded with 2 x 10(5) cells produced approximately 5 x 10(6) neutrophils as opposed to only approximately 3.5 x 10(5) cells with a monocytoid morphology. This predominance of granulocytopoiesis over monocytopoiesis was confirmed by the numbers of cells that had acquired expression of the CD15 antigen and ANAE, which were approximately 2 x 10(6) and 1 x 10(5), respectively. By contrast, parallel cultures containing 100 nM 1 alpha,25-dihydroxyvitamin D3 (VitD3) generated more monocytes than neutrophils. At day 14, VitD3-treated cultures contained approximately 2 x 10(6) cells with morphologies consistent with their differentiation toward monocytes and approximately 1 x 10(6) ANAE-positive cells, compared with approximately 9.5 x 10(5) cells having morphologies of granulocyte-series cells and approximately 4.5 x 10(4) CD15-positive cells. In both control and VitD3-treated cultures, the enzymes cathepsin G and human leukocyte elastase were expressed almost exclusively by cells that were differentiating toward neutrophils. These data reveal that VitD3 promotes monocytopoiesis and suppresses granulocytopoiesis of primitive blast cells.
A E Barton; C M Bunce; R A Stockley; P Harrison; G Brown
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of leukocyte biology     Volume:  56     ISSN:  0741-5400     ISO Abbreviation:  J. Leukoc. Biol.     Publication Date:  1994 Aug 
Date Detail:
Created Date:  1994-09-23     Completed Date:  1994-09-23     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8405628     Medline TA:  J Leukoc Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  124-32     Citation Subset:  IM    
Department of Immunology, Medical School, University of Birmingham, England.
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MeSH Terms
Calcitriol / pharmacology*
Cathepsin G
Cathepsins / physiology
Cell Cycle / drug effects,  physiology
Cell Differentiation / drug effects
Cell Division / drug effects
Cells, Cultured
Granulocytes / cytology*,  drug effects,  enzymology
Hematopoiesis / drug effects*
Hematopoietic Stem Cells / cytology,  drug effects
Leukocyte Elastase
Lymphocyte Activation / drug effects
Models, Biological
Monocytes / cytology*,  drug effects,  enzymology
Pancreatic Elastase / physiology
Phagocytes / drug effects
Serine Endopeptidases
Reg. No./Substance:
32222-06-3/Calcitriol; EC 3.4.-/Cathepsins; EC 3.4.21.-/Serine Endopeptidases; EC protein, human; EC G; EC Elastase; EC Elastase

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