[Platelet factor 4, reversible inhibitor of megakaryocytogenesis, protector of megakaryocytes during chemotherapy].
Development of megakaryocyte (MK) from CD34+ cord blood (CB) cells in both plasma clot culture and liquid culture was significantly inhibited by human platelet factor 4 (PF4) and human transforming growth factor beta 1 (TGF beta 1). Inhibition of cell growth by PF4 was reversible judging from the fact that the CD34+ cells preincubated with PF4 could regenerate colonies after washing and replating into the cultures. By contrast, TGF beta 1-pretreated CD34+ cells gave rise to few colonies following replating. Moreover, incubation of CD34+ cells with PF4 in liquid culture caused an increase in the number of both stem cell factor (SCF)-binding cells and CD34 antigen-bearing cells, and exhibited greater capacity to form MK colonies than control after the treatment of 5-FU. In vivo in mice, twice injections of PF4 at 40 micrograms/kg resulted in a significant increase in the number of colony-forming cells with high proliferative potential (HPP-CFC) and colony-forming unit-megakaryocyte (CFU-MK) in bone marrow. In exponentially growing human erythroleukemia cells (HEL), the addition of PF4 prolonged cell cycle progression and therefore resulted in an increased cell population in S phase, as determined by flow cytometric analysis. Different from PF4, TGF beta 1 blocked more cells in G1 phase. These results demonstrate that PF4 and TGF beta 1 inhibit MK development from CD34+ CB cells by different mechanisms and suggest that PF4, unlike TGF beta 1, exerts its inhibitory effect on cell growth in a reversible and S phase-specific manner by which it protects stem cells and MK progenitor cells from 5-FU cytotoxicity.
Caen
J P
JP
Institut des Vaisseaux et du Sang, Hôpital Lariboisière, Paris.
Xi
X
X
Aidoudi
S
S
Fournier
S
S
Schlegel
N
N
Bellucci
S
S
Han
Z C
ZC
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D008533:Megakaryocytes / Q000187:drug effects*; D051379:Mice; D010978:Platelet Factor 4 / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D016212:Transforming Growth Factor beta; D010978:Platelet Factor 4
Facteur 4 plaquettaire, inhibiteur réversible de la mégacaryocytogénèse, protecteur des mégacaryocytes au cours de la chimiothérapie.