PMID- 7962115 OWN - NLM STAT- MEDLINE DCOM- 19941228 LR - 20061115 IS - 0021-9541 (Print) IS - 0021-9541 (Linking) VI - 161 IP - 2 DP - 1994 Nov TI - Differential effects of transforming growth factor-beta 1 on distinct developmental stages of murine megakaryocytopoiesis. PG - 312-8 AB - 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. FAU - Jackson, H AU - Jackson H AD - Department of Physiology, University of Melbourne, Parkville, Victoria, Australia. FAU - Williams, N AU - Williams N FAU - Westcott, K R AU - Westcott KR FAU - Green, R AU - Green R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Cell Physiol JT - Journal of cellular physiology JID - 0050222 RN - 0 (Transforming Growth Factor beta) SB - IM MH - Animals MH - Cell Division/drug effects MH - Cells, Cultured MH - Hematopoiesis/*drug effects MH - Megakaryocytes/*drug effects/physiology MH - Mice MH - Stem Cells/cytology/drug effects MH - Transforming Growth Factor beta/*pharmacology EDAT- 1994/11/01 00:00 MHDA- 1994/11/01 00:01 CRDT- 1994/11/01 00:00 PHST- 1994/11/01 00:00 [pubmed] PHST- 1994/11/01 00:01 [medline] PHST- 1994/11/01 00:00 [entrez] AID - 10.1002/jcp.1041610216 [doi] PST - ppublish SO - J Cell Physiol. 1994 Nov;161(2):312-8. doi: 10.1002/jcp.1041610216.