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 μg/inj) and in vitro (2.5 and 5 μg/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.