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Vascular endothelial cells and granulopoiesis: interleukin-1 stimulates
release of G-CSF and GM-CSF
KM Zsebo, VN Yuschenkoff, S Schiffer, D Chang, E McCall, CA Dinarello, MA Brown, B Altrock and GC Bagby
Amgen, Thousand Oaks, CA 91320.
Cultured mononuclear phagocytes produce soluble factors that stimulate
endothelial cells to release GM-colony-stimulating activity (GM-CSA). One
such factor was recently identified as interleukin 1 (IL 1). Studies were
designed to determine which types of granulopoietic factors are released by
IL 1-stimulated endothelial cells. Supernatants from endothelial cells
cultured for 3 days in medium containing IL 1 alpha and beta were tested in
both murine and human CFU-GM colony growth assays. The effect of
conditioned media on differentiation of WEHI-3B myelomonocytic leukemic
cells was also examined. Control media containing IL 1 alone or
unstimulated endothelial cell-conditioned media contained no detectable CSA
in any bioassay. Medium conditioned by IL 1-stimulated endothelial cells
stimulated the clonal growth of both human and murine CFU-GM and induced
macrophage differentiation of WEHI-3B cells. Treatment of these conditioned
media with a highly specific neutralizing monoclonal G-CSF antibody
completely inhibited their activity in the murine CFU-GM assay, but only
partially inhibited GM colony growth by human marrow. Treatment of the
active conditioned media with a neutralizing rabbit anti-human GM-CSF
antibody partially reduced the activity of the media in the human GM-colony
growth assay. G-CSF radioimmunoassay of endothelial cell culture
supernatants and Northern blot analysis of endothelial cell cytoplasmic RNA
for GM-CSF gene transcripts confirmed that IL 1 induced expression of both
G-CSF and GM-CSF genes. Because treatment of media with both antibodies
abrogated all activity in the human GM colony growth assay, we conclude
that IL 1-stimulated endothelial cells release both G and GM-CSF and that
these are the only granulopoietic factors detectable in clonogenic assays
released by these cells in vitro.
Volume 71,
Issue 1,
pp. 99-103,
01/01/1988
Copyright © 1988 by The American Society of Hematology
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