Recombinant human megakaryocyte growth and development factor stimulates thrombocytopoiesis in normal nonhuman primates.
Megakaryocyte growth and development factor (MGDF) is a novel cytokine that binds to the c-mpl receptor and stimulates megakaryocyte development in vitro and in vivo. This report describes the ability of recombinant human (r-Hu) MGDF to affect megakaryocytopoiesis in normal nonhuman primates. r-HuMGDF was administered subcutaneously to normal, male rhesus monkeys once per day for 10 consecutive days at dosages of 2.5, 25, or 250 micrograms/kg of body weight. Bone marrow and peripheral blood were assayed for clonogenic activity and peripheral blood counts were monitored. Circulating platelet counts increased significantly (P < .05) for all doses within 6 days of r-HuMGDF administration and reached maximal levels between day 12 and day 14 postcytokine administration. The 2.5, 25.0, and 250.0 micrograms/kg/d doses elicited peak mean platelet counts that were 592%, 670%, and 449% of baseline, respectively. Bone marrow-derived clonogenic data showed significant increases in the concentration of megakaryocyte (MEG)-colony-forming unit (CFU) and granulocyte-erythroid-macrophage-megakaryocyte (GEMM)-CFU, whereas that of granulocyte-macrophage (GM)-CFU and burst-forming unit-erythroid (BFU-e) remained unchanged during the administration of r-HuMGDF. These data show that r-HuMGDF is a potent stimulator of thrombocytopoiesis in the normal nonhuman primate.
Farese
A M
AM
Armed Forces Radiobiology Research Institute, Bethesda, MD 20889-5603, USA.
Hunt
P
P
Boone
T
T
MacVittie
T J
TJ
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D003114:Colony-Forming Units Assay; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects*; D010976:Platelet Count / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D013926:Thrombopoietin / Q000494:pharmacology*
D011994:Recombinant Proteins; D013926:Thrombopoietin