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Inhibition of interleukin 3 and colony-stimulating factor 1-stimulated
marrow cell proliferation by pertussis toxin
YX He, E Hewlett, D Temeles and P Quesenberry
Department of Internal Medicine, University of Virginia School of Medicine,
Charlottesville 22908.
Pertussis toxin (PT) catalyzes the ADP-ribosylation of several guanine
nucleotide-binding (G) proteins that are involved in the transduction of
cell surface receptor-mediated signals. Involvement of such G- proteins in
regulation of hematopoiesis by two growth factors, colony- stimulating
factor-1 (CSF-1) and interleukin 3 (IL 3), was investigated using pertussis
toxin. Continuous or pulse exposure of murine bone marrow cells to
pertussis toxin inhibited CSF-1 or IL 3-induced colony formation by
approximately 50%. Pertussis toxin inhibition was also demonstrated against
partially separated marrow from 5-fluorouracil- treated mice. The toxin
effect was blocked by heating (95 degrees C for 30 minutes), by antitoxin
antibody and was not associated with increased cAMP levels in target cells.
In experiments with murine marrow, toxin-mediated inhibition appeared to
involve predominantly the macrophage lineage. IL 3 stimulation of
proliferation of the murine marrow-derived factor-dependent cell line
FDC-P1, as measured by 3H-TdR incorporation, and CSF-1 stimulation of pure
populations of murine bone marrow derived macrophages, as measured by DNA
content and cell number, was also inhibited. Analysis of the effects of
pertussis toxin on the growth of single cells stimulated by IL 3
demonstrated that this inhibition involved a decreased growth rate rather
than a toxic ablation of cells. Phorbol myristate acetate (PMA) stimulated
FDC-P1 cells and was able to abrogate the PT inhibition of IL 3 stimulation
of these cells, suggesting but not establishing that IL 3 may mediate its
proliferative effects through activating protein kinase C.
Volume 71,
Issue 5,
pp. 1187-1195,
05/01/1988
Copyright © 1988 by The American Society of Hematology
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