A Role for Calmodulin in the Growth of Human Hematopoietic Progenitor Cells

A possible role for calmodulin in the colony growth of human hematopoietic progenitor cells was investigated using pharmacologic approaches. We obtained evidence for a dose-dependent inhibition of colony formation of myeloid progenitor cells (CFU-C) stimulated by interleukin-3 (IL-3), granulocyte-ma...

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Bibliographic Details
Published in:Blood 1990-04, Vol.75 (7), p.1446-1454
Main Authors: Katayama, Naoyuki, Nishikawa, Masakatsu, Komada, Fumihiko, Minami, Nobuyuki, Shirakawa, Shigeru
Format: Article
Language:English
Subjects:
Bone Marrow Cells
Calmodulin - antagonists & inhibitors
Calmodulin - physiology
Cell Division - drug effects
Cell Line
Colony-Stimulating Factors - pharmacology
Granulocyte Colony-Stimulating Factor
Granulocyte-Macrophage Colony-Stimulating Factor
Growth Substances - pharmacology
Hematopoietic Stem Cells - cytology
Hematopoietic Stem Cells - drug effects
Humans
Interleukin-3 - pharmacology
Kinetics
Recombinant Proteins - pharmacology
Sulfonamides - pharmacology
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Summary:A possible role for calmodulin in the colony growth of human hematopoietic progenitor cells was investigated using pharmacologic approaches. We obtained evidence for a dose-dependent inhibition of colony formation of myeloid progenitor cells (CFU-C) stimulated by interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF). or granulocyte CSF (G-CSF) by three calmodulin antagonists, N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide hydrochloride (W-7), N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide hydrochloride (W-13), and trifluoperazine. Chlorine-deficient analogs of W-7 and W-13, with a lower affinity for calmodulin, did not inhibit the growth of CFU-C colonies. W-7, W-13, and trifluoperazine inhibited the colony formation of immature erythroid progenitor cells (BFU-E) stimulated by IL-3 plus erythropoietin (Ep) or GM-CSF plus Ep, in a dose-dependent manner, while they did not affect the colony formation of mature erythroid progenitor cells (CFU-E) induced by Ep. W-7, W-13, and trifluoperazine also led to a dose-dependent inhibition of GM-CSF-induced colony formation of KG-1 cells. Calmodulin-dependent kinase activity derived from the KG-1 cells was inhibited by these three calmodulin antagonists in a dose-dependent manner. These data suggest that calmodulin may play an important regulatory role via a common process in the growth of hematopoietic progenitor cells stimulated by IL-3, GM-CSF, and G-CSF. Mechanisms related to the growth signal of Ep apparently are not associated with calmodulin-mediated systems.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V75.7.1446.1446