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Bone marrow stromal fibroblasts secrete interleukin-6 and granulocyte-
macrophage colony-stimulating factor in the absence of inflammatory
stimulation: demonstration by serum-free bioassay, enzyme-linked
immunosorbent assay, and reverse transcriptase polymerase chain reaction
SC Guba, CI Sartor, LR Gottschalk, YH Jing, T Mulligan and SG Emerson
Department of Internal Medicine, University of Michigan, Ann Arbor.
Bone marrow (BM) stromal fibroblasts produce hematopoietic growth factors
(HGFs) in response to inflammatory mediators such as tumor necrosis
factor-alpha or interleukin-1 alpha (IL-1 alpha). In the absence of such
inflammatory stimuli, production of HGFs by BM stromal cells has been
problematic and controversial. In vivo, however, basal hematopoiesis
maintains blood counts within a normal homeostatic range even in the
absence of inflammation, and HGFs are required for progenitor cell
differentiation in vitro. To better ascertain the contribution of BM
stromal fibroblasts to basal hematopoiesis, we therefore studied HGF
production in quiescent BM stromal fibroblasts by three sensitive assays:
serum-free bioassay, enzyme-linked immunosorbent assay, and reverse
transcriptase polymerase chain reaction. Stromal fibroblasts were cultured
in the presence or absence of normal human serum to determine if serum
factor(s) present in the noninflammatory (basal) state induce secretion of
HGFs. Human serum was found to induce or enhance transcription and
secretion of granulocyte- macrophage colony-stimulating factor (GM-CSF) and
enhance secretion of constitutively expressed IL-6. In contrast, no
secretion of either granulocyte-CSF (G-CSF) or IL-3 was found. These data
indicate that factors in normal human serum are active in enhancing GM-CSF
and IL-6 production by stromal fibroblasts and suggest that these growth
factors contribute to the maintainance of normal, basal hematopoiesis in
vivo.
Volume 80,
Issue 5,
pp. 1190-1198,
09/01/1992
Copyright © 1992 by The American Society of Hematology
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