PURIFICATION AND BIOLOGIC CHARACTERIZATION OF PLASMA-DERIVED MEGAKARYOCYTE GROWTH AND DEVELOPMENT FACTOR

The isolation and cloning of the ligand for the cytokine receptor, Mpl , have been recently described. In this report we present details of t he purification of this novel cytokine (megakaryocyte growth and devel opment factor [MGDF]) from aplastic canine plasma. Two forms of canine MGDF, with apparent molecular weights of 25 kD and 31 kD and sharing a common N-terminal amino acid sequence, were isolated. The sole conta minant detected in purified 25-kD or 31-kD MGDF was canine Ig. Canine MGDF is characterized as a human megakaryocyte colony-stimulating fact or that acts synergistically with human recombinant stem cell factor b ut not interleukin-3. MGDF also appears to be physiologically regulate d in response to platelet demand, In canine and murine models, serum l evels of MODE activity peak during the thrombocytopenic periods after irradiation, 5-fluorouracil, or antiplatelet antisera injections. Thes e data indicate that the megakaryocyte-stimulating activity that accum ulates in plasma in response to platelet losses is a novel cytokine th at functions through an interaction with the Mpl cytokine receptor. (C ) 1995 by The American Society of Hematology.