Carboxy-terminal peptides (C1-24 and C13-24 but not C1-13) of platelet factor 4 inhibit murine megakaryocytopoiesis, an activity which is neutralized by heparin.
Negative regulation of megakaryocytopoiesis is a complex process involving various cytokines. One of these cytokines is platelet factor 4 (PF4), a megakaryocyte/platelet specific protein. PF4 and a carboxy-terminal peptide related to PF4 have been reported to inhibit human and murine megakaryocytopoiesis. The growth of several megakaryoblastic cell lines: human erythroleukaemia cell line (HEL). Meg-01 and Dami, was also inhibited by PF4 and a 13-24 carboxy-terminal peptide related to PF4. We report that peptides corresponding to the 1-24 and 13-24 but not 1-13 carboxy-terminal region of PF4 inhibit murine megakaryocytopoiesis both in vivo (5 micrograms/inj) and in vitro (2.5 and 5 micrograms/ml). Moreover, such an inhibitory activity of PF4-related peptides is abrogated by heparin (5 IU/dish). These overall data indicate that carboxy-terminal PF4-related peptides retain the inhibitory effect of PF4 on both murine single MK and CFU-MK in vivo and in vitro by acting on an early stage of megakaryocytopoiesis and strongly suggest that the inhibitory activity of the multi-functional PF4 might be localized in a short carboxy-terminal region which might include, in part, the PF4 heparin binding domain.
Lebeurier
I
I
Institut des Vaisseaux et du Sang, Hôpital Lariboisière, Paris, France.
Basara
N
N
Aïdoudi
S
S
Amiral
J
J
Caen
J P
JP
Han
Z C
ZC
D000595:Amino Acid Sequence; D000818:Animals; D001854:Bone Marrow Cells; D018929:Cell Culture Techniques; D006493:Heparin / Q000494:pharmacology*; D008297:Male; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology*; D010978:Platelet Factor 4 / Q000494:pharmacology*
D010446:Peptide Fragments; D010978:Platelet Factor 4; D006493:Heparin