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Modulation of human G-CSF receptor mRNA and protein in normal and leukemic myeloid cells by G-CSF and retinoic acid

Granulocyte colony‐stimulating factor (G‐CSF) is produced by several cell types throughout the body and has a variety of effects on neutrophils and their precursors, which are mediated by binding to its receptor. It is not yet known what physiologic factors modulate G‐CSF receptor mRNA expression in...

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Bibliographic Details
Published in:Journal of leukocyte biology 1995-06, Vol.57 (6), p.964-971
Main Authors: Tkatch, Lisa S., Rubin, Kristin A., Ziegler, Steven F., Tweardy, David J.
Format: Article
Language:English
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Summary:Granulocyte colony‐stimulating factor (G‐CSF) is produced by several cell types throughout the body and has a variety of effects on neutrophils and their precursors, which are mediated by binding to its receptor. It is not yet known what physiologic factors modulate G‐CSF receptor mRNA expression in these cells. We studied the effect of G‐CSF on freshly isolated neutrophils and bone marrow cells from normal human subjects and on myeloid leukemic cell lines. We found that G‐CSF receptor mRNA levels were maintained by G‐CSF in neutrophils but not in bone marrow cells. Of the leukemic cell lines tested, K562 and BV173, both of which contain the bcr‐abl translocation, neither expressed G‐CSF receptor mRNA. Whereas G‐CSF did not affect mRNA levels for its receptor in myeloid leukemic cell lines, exposure of the acute promyelocytic cell line, NB4, to all‐trans retinoic acid induced a striking increase in G‐CSF receptor mRNA expression and resulted in increased G‐CSF receptor surface expression. The effect of retinoic acid on G‐CSF receptor mRNA on NB4 cells occurred early, before morphologic evidence of differentiation, and required protein synthesis. All‐trans retinoic acid also up‐regulated G‐CSF receptor mRNA in the myeloid leukemia cell line HL‐60. Thus, maintenance of G‐CSF receptor on neutrophils by G‐CSF may extend the duration of ligand responsiveness. Furthermore, the ability of retinoic acid to up‐regulate G‐CSF receptor may account for the synergistic effect of G‐CSF and retinoic acid in differentiation induction of acute promyelocytic leukemia. J. Leukoc. Biol. 57: 964–971; 1995.
ISSN:0741-5400
1938-3673
DOI:10.1002/jlb.57.6.964