Regulation of hematopoiesis-IV: The role of interleukin-3 and bryostatin 1
in the growth of erythropoietic progenitors from normal and anemic W/Wv
mice
JP Leonard, WS May, JN Ihle, GR Pettit and SJ Sharkis
Johns Hopkins Oncology Center, Baltimore, MD 21205.
We and others have established a role for T lymphocytes and their products
in the regulation of erythropoiesis. Interleukin-3 (IL-3) is a
multipotential lymphokine with burst-promoting activity that is produced by
activated T lymphocytes. In the anemic, stem cell-defective W/Wv mouse we
have described the absence of a functionally active thymocyte population
that in normal animals enhances erythroid progenitor growth and stem cell
self-renewal. In studies reported here we find that W/Wv mouse marrow
responds to exogenous IL-3 by increased erythroid progenitor cell growth.
The BFU-E and CFU-E from anemic donors are more sensitive to IL-3 than are
those in +/+ marrow. We have recently observed a stimulatory effect of
bryostatin 1 (a macrocyclic lactone derived from a marine invertebrate) on
normal erythropoiesis in human bone marrow progenitor assays. To test the
effects of this molecule on murine normal and anemic W/Wv cells we grew
these cells in the presence of increasing doses of bryostatin 1. Bryostatin
mimics the stimulatory action of IL-3 on W/Wv bone marrow. Polyclonal
antibody directed against murine IL-3 blocks the stimulatory effect of
bryostatin on erythropoiesis. Otherwise inactive thymocytes from W/Wv mice
in coculture with W/Wv bone marrow showed stimulation of erythropoiesis in
the presence of bryostatin. We believe that bryostatin may in part act by
stimulating T lymphocytes to release physiologic concentrations of
lymphokines.
Volume 72,
Issue 5,
pp. 1492-1496,
11/01/1988
Copyright © 1988 by The American Society of Hematology
