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Purification and biologic characterization of plasma-derived megakaryocyte
growth and development factor
P Hunt, YS Li, JL Nichol, MM Hokom, JM Bogenberger, SE Swift, JD Skrine, AC Hornkohl, H Lu and C Clogston
Amgen, Inc., Amgen Center, Thousand Oaks, CA 91320, USA.
The isolation and cloning of the ligand for the cytokine receptor, Mpl,
have been recently described. In this report we present details of the
purification of this novel cytokine (megakaryocyte growth and development
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 contaminant
detected in purified 25-kD or 31-kD MGDF was canine Ig. Canine MGDF is
characterized as a human megakaryocyte colony- stimulating factor that acts
synergistically with human recombinant stem cell factor but not
interleukin-3. MGDF also appears to be physiologically regulated in
response to platelet demand. In canine and murine models, serum levels of
MGDF activity peak during the thrombocytopenic periods after irradiation,
5-fluorouracil, or antiplatelet antisera injections. These data indicate
that the megakaryocyte-stimulating activity that accumulates in plasma in
response to platelet losses is a novel cytokine that functions through an
interaction with the Mpl cytokine receptor.
Volume 86,
Issue 2,
pp. 540-547,
07/15/1995
Copyright © 1995 by The American Society of Hematology
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