Thrombospondin-1 inhibits in vitro megakaryocytopoiesis via CD36

Thromb Res. 2003 Jan 1;109(1):47-54. doi: 10.1016/s0049-3848(03)00142-7.


Thrombospondin-1 (TSP-1) is an inhibitor of angiogenesis, inducing apoptosis of the endothelial cells via CD36 signaling mechanism. We investigated CD36 expression and the effect of TSP-1 on megakaryocytopoiesis, with and without pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), and with and without blocking TSP-1 binding with receptor CD36 on megakaryocytic cells. Our data showed that TSP-1 induced a dose-dependent growth inhibition in both murine and human colony forming unit-megakaryocyte (CFU-MK) assays and significantly counteracted the mitogenic effect from PEG-rHuMGDF. Moreover, the growth suppression induced by TSP-1 was correlated with CD36 expression in megakaryocytic cell lines, where growth inhibition was demonstrated in CD36 positive (Meg-01, Dami and CHRF-288-11) but not in CD36 negative (M-07e) cell lines. More importantly, the inhibitory effect of TSP-1 on both human CFU-MK and Meg-01 cells was partially but significantly reversed by the addition of FA6-152 (anti-CD36), a blocking antibody which blocks the access of TSP-1 to CD36 receptor, suggesting that the TSP-1-induced inhibition of megakaryocytopoiesis is probably mediated in part by the binding of TSP-1 to CD36 expressed on the megakaryocytic progenitors. Thus, our findings represent the first demonstration that TSP-1 inhibits in vitro megakaryocytopoiesis via interaction with CD36.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • CD36 Antigens / immunology
  • CD36 Antigens / metabolism
  • CD36 Antigens / physiology*
  • Cell Division / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Hematopoietic Stem Cells / drug effects
  • Humans
  • Mice
  • Platelet Factor 4 / pharmacology
  • Polyethylene Glycols / pharmacology
  • Protein Binding
  • Recombinant Proteins / pharmacology
  • Thrombopoiesis / drug effects*
  • Thrombopoietin / pharmacology
  • Thrombospondin 1 / metabolism
  • Thrombospondin 1 / pharmacology*


  • Antibodies, Monoclonal
  • CD36 Antigens
  • Recombinant Proteins
  • Thrombospondin 1
  • polyethylene glycol-recombinant human megakaryocyte growth and development factor
  • Platelet Factor 4
  • Polyethylene Glycols
  • Thrombopoietin