CARBOXY-TERMINAL PEPTIDES (C1-24 AND C-13-24 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 invol ving various cytokines. One of these cytokines is platelet factor 4 (P F4), a megakaryocyte/platelet specific protein, PF4 and a carboxy-term inal peptide related to PF4 have been reported to inhibit human and mu rine megakaryocytopoiesis. The growth of several megakaryoblastic cell lines: human erythroleukaemia cell line (HEL), Meg-01 and Dami, was a lso inhibited by PF4 and a 13-24 carboxy-terminal peptide related to P F4, We report that peptides corresponding to the 1-24 and 13-24 but no t 1-13 carboxy-terminal region of PF4 inhibit murine megakaryocytopoie sis both in vivo (5 mu g/inj) and in vitro (2.5 and 5 mu g/ml). Moreov er, such an inhibitory activity of PF4-related peptides is abrogated b y heparin (5IU/dish). These overall data indicate that carboxy-termina l PF4-related peptides retain the inhibitory effect of PF4 on both mur ine single MK and CFU-MK in vivo and in vitro by acting on an early st age of megakaryocytopoiesis and strongly suggest that the inhibitory a ctivity of the multi-functional PF4 might be localized in a short carb oxy-terminal region which might include, in part, the PF4 heparin bind ing domain.