Stromal cell-derived factor-1 (SDF-1) acts together with thrombopoietin to enhance the development of megakaryocytic progenitor cells (CFU-MK)

Abstract

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 stem 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.

Stromal cell derived factor-1 acutely promotes neural progenitor cell proliferation in vitro by a mechanism involving the ERK1/2 and PI-3K signal pathways☆

“…There are other reports that SDF-1 stimulates proliferation in such cell types as murine pre-B cells, human hematopoietic progenitors, etc. (Hodohara et al, 2000;Rosu-Myles and Bhatia, 2003), implying a comparably extensive nutritional and proliferative function for this chemokine. Besides stimulation of cell proliferation, ERK1/2 and PI-3 kinase are also traditionally believed to promote cell survival (Chang and Karin, 2001;Brunet et al, 1999).…”

Stromal cell‐derived factor‐1α induces astrocyte proliferation through the activation of extracellular signal‐regulated kinases 1/2 pathway

“…However, these animals show normal T lymphopoiesis (Nagasawa et al 1996a;Tachibana et al 1998;Zou et al 1998). More recently, it was found that SDF-1 and CXCR4 may play a critical role in the engraftment of haematopoietic stem cells to bone marrow and also in the platelet formation (Hamada et al 1998;Wang et al 1998;Peled et al 1999;Hodohara et al 2000;Kowalska et al 2000).…”

Thrombopoietin‐induced CXC chemokines, NAP‐2 and PF4, suppress polyploidization and proplatelet formation during megakaryocyte maturation

“…The megakaryocyte progenitors, c-Kit + CD41 + cells, were prepared as described (Hodohara et al 2000). Lineage-negative bone marrow cells prepared from BDF1 mice were incubated with fluorescein isothiocyanate (FITC)-conjugated anti-mouse CD41 antibody (BD Pharmingen, San Diego, CA) and APC-conjugated anti-mouse CD117 (c-Kit) antibody (BD Pharmingen) for 1 h on ice.…”

“…1998). Interestingly, it was recently reported that SDF-1 stimulated megakaryocyte colony formation in the presence of TPO (Hodohara et al . 2000) and enhanced polyploidization as well as PPF of CD34 + progenitors in the presence of TPO (Guerriero et al .…”