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 megakaryocyt e-platelet protein, is a potent inhibitor of human and murine megakary ocytopoiesis. 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 form ing cells (HPP-CFC), colony-forming-unit megakaryocyte (CFU-MK) and co lony-forming unit granulocyte-macrophage (CFU-GM) progenitor number, e ight days after 5-FU administration, when it was given intraperitoneal ly twice a day (200 mu g/kg/inj) prior to 5-FU administration (150 mg/ kg). Furthermore, the C13-24DE pretreatment enhanced both the number a nd the diameter of single megakaryocyte (MK) by day 8. These data indi cate that the C13-24DE peptide related to PF4 accelerated the in vivo recovery of stem cells, progenitors (CFU-GM, CFU-MK) and single MK aft er 5-FU treatment and may have a hemoprotective effect against chemoth erapeutic agents. (C) 1997 Elsevier Science Ireland Ltd.