A role for calmodulin in the growth of human hematopoietic progenitor cells
N Katayama, M Nishikawa, F Komada, N Minami and S Shirakawa
Second Department of Internal Medicine, Mie University School of Medicine,
Tsu, Japan.
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.
Volume 75,
Issue 7,
pp. 1446-1454,
04/01/1990
Copyright © 1990 by The American Society of Hematology
