A 13-24 C-terminal peptide related to PF4 accelerates hematopoietic recovery of progenitor cells in vivo in mice treated with 5-fluorouracil.

We have recently reported that platelet factor 4 (PF4), a megakaryocyte-platelet protein, is a potent inhibitor of human and murine megakaryocytopoiesis. In addition, PF4 accelerated the recovery of the marrow precursor cells in 5-fluorouracil (5-FU) treated mice. We show in this study that a slight modification of the C-terminal peptide related to PF4 (C13-24DE), which was previously reported as the carboxy terminal region of PF4 implicated in PF4 inhibitory activity, is also able to significantly increase murine high proliferating-potential-colony forming cells (HPP-CFC), colony-forming-unit megakaryocyte (CFU-MK) and colony-forming unit granulocyte-macrophage (CFU-GM) progenitor number, eight days after 5-FU administration, when it was given intraperitoneally twice a day (200 micrograms/kg/inj) prior to 5-FU administration (150 mg/kg). Furthermore, the C13-24DE pretreatment enhanced both the number and the diameter of single megakaryocyte (MK) by day 8. These data indicate that the C13-24DE peptide related to PF4 accelerated the in vivo recovery of stem cells, progenitors (CFU-GM, CFU-MK) and single MK after 5-FU treatment and may have a hemoprotective effect against chemotherapeutic agents.