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Recombinant human interleukin-3 stimulation of hematopoiesis in humans:
loss of responsiveness with differentiation in the neutrophilic myeloid
series
AF Lopez, PG Dyson, LB To, MJ Elliott, SE Milton, JA Russell, CA Juttner, YC Yang, SC Clark and MA Vadas
Division of Human Immunology, Institute of Medical and Veterinary Science,
Adelaide, South Australia.
Recombinant human (rh) interleukin-3 (IL-3) stimulated the proliferation
and differentiation of erythroid, granulocyte, macrophage, eosinophil (Eo),
and mixed colonies as well as megakaryocytes from human bone marrow cells.
rh IL-3 was a weaker stimulus than rh granulocyte-macrophage
colony-stimulating factor (GM- CSF) for day 14 myeloid cell colonies. At
day 7 of incubation, rh IL-3 stimulated a few G, M, and Eo clusters but no
colonies. This loss of responsiveness of myeloid cells to rh IL-3 was
accentuated with further differentiation of the cells. rh IL-3 stimulated
very few or no clones after five-day incubation with enriched promyelocytes
and myelocytes, whereas rh GM-CSF was an efficient stimulus. Responsiveness
to rh IL-3 was completely lost in postmitotic mature neutrophils.
Incubation of these cells with rh IL-3 did not result in enhanced
antibody-dependent cell-mediated cytotoxicity (ADCC) of tumor cells or
superoxide anion production after stimulation with
formyl-methyl-leucyl-phenylalanine (FMLP), although they could be
stimulated by rh GM-CSF. In addition, preincubation of neutrophils with
different concentrations of rh IL-3 failed to increase or decrease their
response to rh GM-CSF. In contrast to neutrophils, mature Eos could be
stimulated by rh IL-3 to kill antibody-coated tumor cells. These results
show that cells of the neutrophilic myeloid series lose their
responsiveness to h IL-3 as they differentiate and suggest that although h
IL-3 may be an important therapeutic agent to use for hematopoietic
regeneration in vivo, the lack of stimulation of mature neutrophil function
makes it an unlikely sole candidate as adjunct therapy for treatment of
infectious diseases.
Volume 72,
Issue 5,
pp. 1797-1804,
11/01/1988
Copyright © 1988 by The American Society of Hematology
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