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Biosynthetic (recombinant) human granulocyte-macrophage colony- stimulating
factor: effect on normal bone marrow and leukemia cell lines
M Tomonaga, DW Golde and JC Gasson
To examine the biologic properties of the molecule encoded by the human
gene for granulocyte-macrophage colony-stimulating factor (GM-CSF), we
expressed the cloned complementary DNA (cDNA) in transfected monkey COS
cells and purified the resultant protein. Purified biosynthetic human
GM-CSF was added to cultures of normal hematopoietic progenitor cells in
semisolid media, and the resulting colonies were characterized
cytochemically. Non-adherent light-density bone marrow cells from healthy
adult volunteers were maximally stimulated with GM-CSF (approximately 250
pmol/L, and four types of colonies were consistently identified by
aspirating the individual colonies and staining with a triple stain for
specific and nonspecific esterases and eosinophilic granules. Pure
neutrophilic granulocyte (G), mixed granulocyte- macrophage (GM), pure
macrophage (M), and pure eosinophil (EO) colonies were observed, the mean
incidences on day 8 being 70%, 20%, 5%, and 5%, and on day 14, 7.5%, 16.6%,
50.9%, and 25.0%, respectively. In all types of colonies, complete
maturation to segmented forms or typical macrophages was detected. GM-CSF
did not enhance the growth of BFU-E from normal peripheral blood buffy coat
cells in the simultaneous presence of erythropoietin alone or
erythropoietin with purified erythroid-potentiating activity. GM-CSF
stimulated HL-60 and KG-1 colony formation twofold and fivefold,
respectively; consistent differentiation induction towards monocytic and
eosinophilic lineages was observed in HL-60 but not in KG-1. These in vitro
findings indicate that GM-CSF is a multilineage stimulator for progenitor
cells of G, GM, M, and EO colonies.
Volume 67,
Issue 1,
pp. 31-36,
01/01/1986
Copyright © 1986 by The American Society of Hematology
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