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.
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.
Mielcarek
M
M
Program in Transplantation Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.
Roecklein
B A
BA
Torok-Storb
B
B
D001853:Bone Marrow / Q000378:metabolism*; D001854:Bone Marrow Cells; D002461:Cell Line, Transformed; D002469:Cell Separation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003238:Connective Tissue / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000737:chemistry; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism* / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D007937:Leukapheresis; D018950:Lipopolysaccharide Receptors; D011994:Recombinant Proteins / Q000494:pharmacology
D017077:Culture Media, Conditioned; D007375:Interleukin-1; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor