Differential effects of transforming growth factor-β1 on distinct developmental stages of murine megakaryocytopoiesis

✍ Scribed by Heather Jackson; Neil Williams; Keith R. Westcott; Ralph Green

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 788 KB
• Volume: 161
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041610216

✦ Synopsis

The effect of transforming growth factor-pl (TGFP1) on three developmental stages of megakaryocytopoiesis was investigated. Using a murine bone marrow agar culture system, titrated doses of TGFPl were added to cultures assaying primitive high pro1 iferative 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-I, 3 and 6 (IL-1 + IL-3 + IL-6) for colony detection was abrogated by the addition of 1 ng TGFPllml. The sensitivity of committed megakaryocyte progenitors (colony-forming unit-megakaryocyte, CFU-Mk) to TGFPl depended on the growth factor combination. TGFPl (1 ngiml) completely inhibited niegakaryocyte colony formation from CFU-Mk only in cultures stimulated by low doses of IL-3. TGFPl ( > l o 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. TGFPl inhibited both IL-?-dependent and IL-6-dependent megakaryocyte growth but tenfold higher doses of TGFPl were required to inhibit growth generated by the combination of IL-3 + 11.-6. The data showed that the capacity of TGFPl to inhibit distinct differentiation stages of the megakaryocytopoietic lineage depended on the concentration and combination of growth factors involved. cc) 1994 WiIcy-Liss, Inc.