Stimulation of human hematopoietic progenitor cell proliferation and differentiation by recombinant human interleukin 3. Comparison and interactions with recombinant human granulocyte-macrophage and granulocyte colony-stimulating factors.
Recombinant human interleukin 3 (IL3) produced in Escherichia coli was purified and its activities examined in cultures of highly enriched human bone marrow progenitor cells. Human IL3 stimulated multipotential (CFU-GEMM) and erythroid (BFU-E) progenitor cells, generating 95% more BFU-E than recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). No further enhancement of BFU-E or CFU-GEMM occurred when IL3 and GM-CSF were used in combination. Human IL3 was more effective than GM-CSF in stimulating granulocyte-macrophage colony-forming cells (CFU-GM) in short-term suspension cultures, but did not induce an increase of CFU-GM, BFU-E, or CFU-GEMM above input levels. IL3 was more active on day-14 (d14) than on d7 CFU-GM, similar to GM-CSF, but generated fewer and smaller CFU-GM-derived clones than either GM-CSF or granulocyte CSF (CI-CSF). The simultaneous addition of plateau levels of IL3 and GM-CSF resulted in an infra-additive augmentation of d7 and d14 CFU-GM-derived clones, whereas IL3 and G-CSF enhanced the number and cellularity predominantly of d14 CFU-GM. In liquid cultures, IL3 induced a greater than 100-fold increase in the number of basophil-mast-like cells and eosinophils and allowed maintenance of these cultures for up to 7 weeks. Human GM-CSF was an almost equally potent, stimulus of eosinophil development but had only a marginal effect on basophilic precursors, whereas G-CSF lacked both activities. Therefore, human IL3 is a multilineage hemopoietic growth factor whose activities appear to encompass and extend beyond those of GM-CSF.
Ottmann
O G
OG
Department of Hematopoietic Regulation, Sloan Kettering Institute, NY 10021.
Abboud
M
M
Welte
K
K
Souza
L M
LM
Pelus
L M
LM
D000328:Adult; D001491:Basophils / Q000502:physiology; D001853:Bone Marrow; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002469:Cell Separation; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D004347:Drug Interactions; D004804:Eosinophils / Q000502:physiology; D004920:Erythropoiesis / Q000187:drug effects; D005109:Extracellular Matrix / Q000502:physiology; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D008407:Mast Cells / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology*; D013535:Suspensions
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007377:Interleukin-3; D011994:Recombinant Proteins; D013535:Suspensions; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor