Differential effects of transforming growth factor-beta 1 on distinct developmental stages of murine megakaryocytopoiesis.
The effect of transforming growth factor-beta 1 (TGF beta 1) on three developmental stages of megakaryocytopoiesis was investigated. Using a murine bone marrow agar culture system, titrated doses of TGF beta 1 were added to cultures assaying primitive high proliferative megakaryocyte progenitors, committed megakaryocyte precursors, and nondividing, endoreduplicating megakaryocytes. The growth of high proliferative megakaryocyte colony-forming cells (HPP-CFU-Mk) that require the growth factors interleukins-1, 3 and 6 (IL-1 + IL-3 + IL-6) for colony detection was abrogated by the addition of 1 ng TGF beta 1/ml. The sensitivity of committed megakaryocyte progenitors (colony-forming unit-megakaryocyte, CFU-Mk) to TGF beta 1 depended on the growth factor combination. TGF beta 1 (1 ng/ml) completely inhibited megakaryocyte colony formation from CFU-Mk only in cultures stimulated by low doses of IL-3. TGF beta 1 (> 10 ng/ml) could only marginally inhibit megakaryocyte colony formation generated in the presence of either high doses of IL-3 or the combination of low dose IL-3 + IL-6. TGF beta 1 inhibited both IL-3-dependent and IL-6-dependent megakaryocyte growth but tenfold higher doses of TGF beta 1 were required to inhibit growth generated by the combination of IL-3 + IL-6. The data showed that the capacity of TGF beta 1 to inhibit distinct differentiation stages of the megakaryocytopoietic lineage depended on the concentration and combination of growth factors involved.
Department of Physiology, University of Melbourne, Parkville, Victoria, Australia.
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Jackson
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Williams
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Westcott
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Green
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006410:Hematopoiesis / Q000187:drug effects*; D008533:Megakaryocytes / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016212:Transforming Growth Factor beta