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Characterization of murine bone marrow and spleen-derived stromal cells:
analysis of leukocyte marker and growth factor mRNA transcript levels
JM Gimble, C Pietrangeli, A Henley, MA Dorheim, J Silver, A Namen, M Takeichi, C Goridis and PW Kincade
Oklahoma Research Foundation, Oklahoma City 73104.
Stromal cells are believed to regulate lympho-hematopoiesis through direct
cell-cell interactions and the release of growth factors. Many questions
remain, however, about their lineage derivation and functional
heterogeneity. We previously prepared a panel of stromal cell lines from
murine spleen and bone marrow and characterized them based on their ability
to support lymphocyte growth in long-term cultures. These cells are now
compared with respect to their expression of various immunoglobulin
superfamily and cytokine genes by Northern blot analysis. These results
indicate that although stromal cells appear to be mesodermal in origin,
they are not closely related developmentally to the hematopoietic
progenitor cells they support. The potential production of at least six
cytokines was demonstrated. All clones constitutively expressed mRNA for
macrophage colony stimulating factor, interleukin-6, transforming growth
factor beta and neuroleukin. The most potent lymphocyte supporting clones
also made interleukin 7 constitutively. Previous findings had suggested
that these clones responded to exogenous stimuli and this has now been
demonstrated in terms of induced expression of IL-6 and G/M-CSF mRNA.
Interleukin 6 mRNA levels were markedly upregulated by exposure of cells to
LPS, TNF, IL-1, IL-6, IL-7, and EGF. G/M-CSF mRNA levels were
"superinduced" by the combination of LPS and cycloheximide, a protein
synthesis inhibitor. These responses are similar to ones documented by
investigators working with endothelial cells and fibroblasts. Together,
these data suggest that stromal cells are a multifunctional component of
the lymphopoietic microenvironment and may be active participants in a
complex, cytokine-mediated regulatory network.
Volume 74,
Issue 1,
pp. 303-311,
07/01/1989
Copyright © 1989 by The American Society of Hematology

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