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CD14+ cells in granulocyte colony-stimulating factor (G-CSF)-mobilized
peripheral blood mononuclear cells induce secretion of interleukin-6 and
G-CSF by marrow stroma
M Mielcarek, BA Roecklein and B Torok-Storb
Program in Transplantation Biology, Fred Hutchinson Cancer Research Center,
Seattle, WA 98104, USA.
The ability of granulocyte colony-stimulating factor (G-CSF)-mobilized
peripheral blood mononuclear cells (G-PBMCs) to induce secretion of
cytokines in primary long-term marrow cultures (LTC) or in the human marrow
stromal cell line HS23 was compared with that of marrow mononuclear cells.
Equal numbers of G-PBMCs or marrow mononuclear cells were added to stromal
cultures, supernatants were harvested at day 4 and levels of interleukin-1
alpha (IL-1 alpha), IL-1 beta, IL-2, IL-6, G-CSF, and tumor necrosis factor
alpha (TNF alpha) were determined. G- PBMCs induced 21.4-fold higher levels
of IL-6 and 12.5-fold higher levels of G-CSF in LTC cocultures compared
with marrow mononuclear cells and induced 20.6-fold more IL-6 and 6.3-fold
more G-CSF when added to HS23 cells. Experiments using sorted populations
of CD20+, CD3+, and CD14+ cells showed that CD14+ cells within G-PBMCs were
responsible for triggering the production of IL-6 and G-CSF. The effect did
not require cell-cell contact and was inhibited when neutralizing
antibodies to IL-1 alpha and IL-1 beta were used in combination. In these
experiments, the greater stimulating ability of G-PBMCs is most likely
attributable to the greater number of CD14+ cells in G-PBMCs (26.1+% +/-
2.3%) compared with marrow (2.5% +/- 0.8%), because equal numbers of CD14+
cells sorted from marrow and G-PBMCs showed comparable ability to induce
IL-6 and G-CSF when placed directly on stromal cells.
Volume 87,
Issue 2,
pp. 574-580,
01/15/1996
Copyright © 1996 by The American Society of Hematology
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