Stromal cell-derived factor-1 (SDF-1) acts together with thrombopoietin to enhance the development of megakaryocytic progenitor cells (CFU-MK)
In: Blood, Jg. 95 (2000), Heft 3, S. 769-775
Online
academicJournal
- print, 47 ref
Zugriff:
Stromal cell-derived factor-1 (SDF-1) is a CXC chemokine that acts as a stimulator of pre-B lymphocyte cell growth and as a chemoattractant for T cells, monocytes, and hematopoietic stem cells. More recent studies also suggest that megakaryocytes migrate in response to SDF-1. Because genetic elimination of SDF-1 or its receptor lead to marrow aplasia, we investigated the effect of SDF-1 on megakaryocyte progenitors (colony-forming units-megakaryocyte [CFU-MK]). We report that SDF-1 augments the growth of CFU-MK from whole murine bone marrow cells when combined with thrombopoietin (TPO). The addition of SDF-1 to interleukin-3 (IL-3) or stern cell factor (SCF) had no effect. Specific antagonists for CXCR4 (the sole receptor for SDF-1 ), T22, and 1-9 (P2G) SDF-1 reduced megakaryocyte colony growth induced by TPO alone, suggesting that many culture systems contain endogenous levels of the chemokine that contributes to the TPO effect. To examine whether SDF-1 has direct effects on CFU-MK, we developed a new protocol to purify megakaryocyte progenitors. CFU-MK were highly enriched in CD41high c-kithigh cells generated from lineage-depleted TPO-primed marrow cells. Because the growth-promoting effects of SDF-1 were also observed when highly purified populations of CFU-MK were tested in serum-free cultures, these results suggest that SDF-1 directly promotes the proliferation of megakaryocytic progenitors in the presence of TPO, and in this way contributes to the favorable effects of the bone marrow microenvironment on megakaryocyte development.
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Stromal cell-derived factor-1 (SDF-1) acts together with thrombopoietin to enhance the development of megakaryocytic progenitor cells (CFU-MK)
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Autor/in / Beteiligte Person: | HODOHARA, K ; FUJII, N ; YAMAMOTO, N ; KAUSHANSKY, K |
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Zeitschrift: | Blood, Jg. 95 (2000), Heft 3, S. 769-775 |
Veröffentlichung: | Washington, DC: The Americain Society of Hematology, 2000 |
Medientyp: | academicJournal |
Umfang: | print, 47 ref |
ISSN: | 0006-4971 (print) |
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