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Effects of recombinant human granulocyte colony-stimulating factor (CSF),
human granulocyte macrophage-CSF, and gibbon interleukin-3 on hematopoiesis
in human long-term bone marrow culture
LH Coutinho, A Will, J Radford, R Schiro, NG Testa and TM Dexter
Department of Experimental Haematology, Paterson Institute for Cancer
Research, Christie Hospital and Radium Institute, Manchester, UK.
We have studied the effects of recombinant human granulocyte colony-
stimulating factor (rhG-CSF), hG macrophage-CSF (hGM-CSF), and gibbon
interleukin-3 (gIL-3) on cell proliferation and differentiation in human
long-term bone marrow culture (LTBMC). hG-CSF induced a maximal increase of
2.3-fold in both total nonadherent cells and GM cluster- forming cells, but
only an increase of 1.7-fold in GM-colony-forming cell (GM-CFC) numbers,
influencing mainly neutrophil differentiation. Cultures treated with
hGM-CSF demonstrated a peak of 12.8-, 21- and 3.2- fold elevations in total
nonadherent cells, cluster, and GM-CFC, respectively, and influenced
differentiation of neutrophils, monocytes, eosinophils, and lymphocytes.
Cultures treated with gIL-3 demonstrated the largest expansion in the
GM-CFC population, reaching a maximum of 5.3-fold in relation to that of
unstimulated controls. IL-3 treatment also increased the numbers of GM
clusters and mature cells (including all myeloid cells and lymphocytes)
7.8- and 4.8-fold, respectively. Similar quantitative and qualitative
changes were induced by G-CSF, GM- CSF, and IL-3 in LTBMCs of patients in
remission after treatment for acute lymphoblastic leukemia or Hodgkin's
lymphoma. Overall, the expansion of GM progenitor cells in cultures treated
with growth factors was larger in the adherent cell layer than in the
nonadherent cell fraction. In addition, hGM-CSF, gIL-3, and hG-CSF to a
less extent, increased the cycling rates of GM-CFC progenitors located in
the adherent layer. These results indicate that hG-CSF is a much less
potent stimulus of hematopoiesis in LTBMC than the other CSFs assayed, and
that the increases in cell production after treatment with G-CSF, GM-CSF,
or IL-3 may be achieved by primary expansion of different cell populations
within the hierarchy of the hematopoietic system. The effects of the growth
factors were transient and the longevity of hematopoiesis in the cultures
was not altered, suggesting that treatment with IL-3, GM-CSF, or G-CSF had
not compromised the ability of primitive cells to give rise to mature
cells. This indicates that the stromal microenvironment in LTBMC can
override potential differentiation-inducing activities of the CSFs.
Volume 75,
Issue 11,
pp. 2118-2129,
06/01/1990
Copyright © 1990 by The American Society of Hematology
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