Further examination of the effects of recombinant cytokines on the
proliferation of human megakaryocyte progenitor cells
E Bruno, RJ Cooper, RA Briddell and R Hoffman
Department of Medicine, Indiana University School of Medicine,
Indianapolis.
The effect of several recombinant cytokines, including interleukin-3
(IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL- 6,
and IL-1 alpha, on megakaryocyte (MK) colony formation by a normal human
bone marrow subpopulation (CD34+ DR+), enriched for the MK colony- forming
unit (CFU-MK), was studied using a serum-depleted, fibrin clot culture
system. IL-3 and GM-CSF, but not IL-6 or IL-1 alpha, stimulated MK colony
formation by CD34+ DR+ cells. However, the addition of IL-1 alpha to CD34+
DR+ cultures containing IL-6 resulted in the appearance of CFU-MK-derived
colonies, suggesting that IL-6 requires the presence of IL-1 alpha to
exhibit its MK colony-stimulating activity (MK-CSA). Addition of
neutralizing antibodies to IL-3 and GM-CSF, but not to IL-6 and IL-1 alpha,
specifically inhibited the MK-CSA of IL-3 and GM-CSF, respectively. The
addition of either anti-IL-6, anti-IL-1 alpha, or anti-IL-3 antisera to
cultures containing both IL-6 and IL-1 alpha totally abolished the MK-CSA
of the IL-6/IL-1 alpha combination. However, neither anti-IL-3 nor
anti-GM-CSF antisera could totally neutralize the additive effect of the
combination of IL-3 and GM-CSF on MK colony formation, indicating that
these two cytokines act by affecting distinct effector pathways. These
results suggest that while IL-3 and GM-CSF can directly affect
CFU-MK-derived colony formation, IL- 1 alpha and IL-6 act in concert to
promote de novo elaboration of IL-3 and thereby promote CFU-MK
proliferative capacity.
Volume 77,
Issue 11,
pp. 2339-2346,
06/01/1991
Copyright © 1991 by The American Society of Hematology
