Thrombospondin, a negative modulator of megakaryocytopoiesis

J Lab Clin Med. 1997 Feb;129(2):231-8. doi: 10.1016/s0022-2143(97)90144-x.


The effects of native thrombospondin (TSP), an 18 kd recombinant protein comprising residues 1-174 of TSP (TSP1-174) with heparin-binding domain and a fusion protein comprising residues 559-669 of TSP (TSP559-669) on murine hematopoiesis, were studied by using different in vitro culture systems. TSP by itself did not show an inhibitory effect on colony-forming unit-megakaryocyte (CFU-MK) growth in a serum-free agar system and on the growth of colony-forming unit-granulocyte and macrophage (CFU-GM) in a plasma clot system. It was, however, found that in the plasma clot culture system when using aplastic anemia serum as the source of thrombopoietin or C-Mpl ligand (TPO), TSP and TSP1-174, but not TSP559-669, were able to inhibit the growth of CFU-MK from unfractionated and lineage negative (Lin-) bone marrow cells in a dose-dependent manner. A statistically significant suppression was seen at 1 microg/ml of TSP and 5 microg/ml of TSP1-174. This inhibitory effect of TSP was further found in both the serum-free agar system and the plasma clot system without aplastic anemia serum, where megakaryocyte colony growth was stimulated by recombinant TPO, basic fibroblast growth factor (bFGF), or interleukin-3 (IL-3). In a methylcellulose system, where a combination of stem cell factor (SCF), IL-3, and granulocyte/macrophage colony-stimulating factor (GM-CSF) were used, TSP inhibited the growth of colony-forming unit-granulocyte-erythroblast, megakaryocyte, and macrophage (CFU-GEMM) but not CFU-GM and burst-forming unit-erythroblast (BFU-E). Interestingly, this inhibitory effect of TSP on megakaryocyte colony growth could be counteracted by Fraxiparin, a low-molecular-weight heparin. These results demonstrate that TSP is a negative modulator of megakaryocytopoiesis and suggest that its inhibitory effect is at least partially mediated by N-terminal heparin-binding domain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division / drug effects
  • Cells, Cultured
  • Granulocytes / cytology
  • Granulocytes / drug effects
  • Hematopoiesis / drug effects*
  • Hematopoietic Stem Cells / cytology
  • Megakaryocytes / drug effects*
  • Membrane Glycoproteins / pharmacology*
  • Mice
  • Mice, Inbred BALB C
  • Peptide Fragments / pharmacology
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Thrombospondins


  • Membrane Glycoproteins
  • Peptide Fragments
  • Thrombospondins