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Human interleukin-4 enhances stromal cell-dependent hematopoiesis:
costimulation with stem cell factor
U Keller, MJ Aman, G Derigs, C Huber and C Peschel
Department of Medicine, Johannes-Gutenberg-University School of Medicine,
Mainz, Germany.
Interleukin-4 (IL-4) has distinct hematopoietic activities, primarily as a
costimulant with other cytokines to enhance colony formation of
hematopoietic progenitors. We investigated the influence of IL-4 on stromal
cell-supported long-term cultures (LTCs) of normal human bone marrow.
Addition of IL-4 to LTCs of unseparated bone marrow or highly enriched
CD34+ cells resulted in a significant increase of myeloid progenitors in
the nonadherent, as well as in the stromal cell-adherent cell populations.
In contrast, the total cell number was not influenced by IL-4, suggesting a
selective effect on primitive progenitor cells. Cord blood cells or CD34+
bone marrow cells were incubated with stem cell factor (SCF) and/or IL-4 in
stromal cell-free cultures. In these experiments, a twofold to fivefold
increase of myeloid progenitor cells was observed in the presence of SCF
and IL-4 as compared with SCF alone. Preincubation of the stromal cell
cultures with IL-4 resulted in an enhanced adherence of CD34+ cells to the
stromal layer. Secretion of hematopoietic growth factors produced by the
stromal cells, such as granulocyte-macrophage colony-stimulating factor
(G-CSF), and IL-1, was inhibited by IL-4. Thus, the increase of
hematopoietic progenitors in LTCs, as observed in the presence of IL-4, can
be at least partially explained by a costimulation of SCF and IL-4 on
primitive progenitor cells and by an enhancement of hematopoietic cells to
stroma. The downregulation of CSFs by IL-4 might prevent the expansion of
the mature hematopoietic cell compartment.
Volume 84,
Issue 7,
pp. 2189-2196,
10/01/1994
Copyright © 1994 by The American Society of Hematology
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