Abstract

Our laboratory has already documented that extracts of urine from aplastic anemia patients stimulate megakaryocyte and platelet production in vivo in rats and mice. This stimulatory activity was apparently mediated by a unique cytokine. This report describes the purification of the factor likely responsible for this activity because it stimulates megakaryocyte colony formation (CFU-meg) in vitro. The factor, when purified to homogeneity, exhibits a molecular weight of 55,000–57,000 and an isoelectric point of 7.2–7.4. Under physiological conditions, ultrafiltration experiments indicate that human megakaryocyte colony-stimulating factor (hMeg-CSF) exists as a monomer or dimer. In contrast to human urinary erythropoietin (Epo), only a small amount of hMeg-CSF forms complexes of high molecular weight aggregates. In contrast to interleukin (IL)-3, hMeg-CSF induces small colonies in vitro containing three to five megakaryoblasts. Even at concentrations 100-fold greater than the threshold amount required to stimulate CFU-meg colony formation, hMeg-CSF stimulated only CFU-meg colonies, but did not stimulate myeloid or erythroid lineage colonies. We propose that this purified factor is specific for the megakaryocyte lineage, and that it be termed human Meg-CSF.

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