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.
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.
Leonard
J P
JP
Johns Hopkins Oncology Center, Baltimore, MD 21205.
May
W S
WS
Ihle
J N
JN
Pettit
G R
GR
Sharkis
S J
SJ
D000818:Animals; D000937:Antigen-Antibody Reactions; D001853:Bone Marrow / Q000502:physiology; D054713:Bryostatins; D003114:Colony-Forming Units Assay; D004920:Erythropoiesis / Q000187:drug effects*; D005260:Female; D066298:In Vitro Techniques; D007377:Interleukin-3 / Q000494:pharmacology*; D007783:Lactones / Q000494:pharmacology*; D018942:Macrolides; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D013950:Thymus Gland / Q000166:cytology
D054713:Bryostatins; D007377:Interleukin-3; D007783:Lactones; D018942:Macrolides; C046785:bryostatin 1