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-macrophage colony-stimulating factor (GM-CSF), or granulocyte CSF (G-CSF) by three calmodulin antagonists, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide 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.
Second Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan.
N
N
Katayama
M
M
Nishikawa
F
F
Komada
N
N
Minami
S
S
Shirakawa
D001854:Bone Marrow Cells; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D007700:Kinetics; D011994:Recombinant Proteins / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology*
D002147:Calmodulin; D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007377:Interleukin-3; D011994:Recombinant Proteins; D013449:Sulfonamides; D016179:Granulocyte Colony-Stimulating Factor; C017967:W 7; C034700:N-(6-aminohexyl)-1-naphthalenesulfonamide; C033772:N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor