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Augmented production of interleukin-6 by normal human osteoblasts in
response to CD34+ hematopoietic bone marrow cells in vitro
RS Taichman, MJ Reilly, RS Verma and SG Emerson
Department of Periodontics, Prevention, Geriatrics, University of Michigan
School of Dentistry, Ann Arbor 48109-1078, USA.
Based on anatomic and developmental findings characterizing hematopoietic
cells in close approximation with endosteal cells, we have begun an
analysis of osteoblast/hematopoietic cell interactions. We explore here the
functional interdependence between these two cell types from the standpoint
of de novo cytokine secretion. We determined that, over a 96-hour period,
CD34+ bone marrow cells had no significant effect on osteoblast secretion
of granulocyte colony-stimulating factor, granulocyte-macrophage
colony-stimulating factor, or transforming growth factor-beta1, but in some
experiments minor increases in leukemia inhibitory factor levels were
observed. However, when CD34+ bone marrow cells were cocultured in direct
contact with osteoblasts, a 222% +/- 55% (range, 153% to 288%) augmentation
in interleukin-6 (IL-6) synthesis was observed. The accumulation of IL-6
protein was most rapid during the initial 24-hour period, accounting for
nearly 55% of the total IL-6 produced by osteoblasts in the absence of
blood cells and 77% of the total in the presence of the CD34+ cells.
Cell-to-cell contact does not appear to be required for this activity, as
determined by coculturing the two cell types separated by porous
micromembranes. The identity of the soluble activity produced by the CD34+
cells remains unknown, but is not likely due to IL-1beta or tumor necrosis
factor-alpha, as determined with neutralizing antibodies. To our knowledge,
these data represent the first demonstration that early hematopoietic cells
induce the production of molecules required for the function of normal bone
marrow microenvironments, in this case through the induction of
hematopoietic cytokine (IL-6) secretion by osteoblasts.
Volume 89,
Issue 4,
pp. 1165-1172,
02/15/1997
Copyright © 1997 by The American Society of Hematology
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