Erythroid burst-promoting activity produced by interleukin-1-stimulated
endothelial cells is granulocyte-macrophage colony-stimulating factor
GM Segal, E McCall and GC Bagby
Department of Medicine, Oregon Health Sciences University, Portland.
Interleukin-1 (IL-1) induces cultured human umbilical vein endothelial
cells to elaborate heterogeneous hematopoietic growth factors, including
granulocyte-macrophage and granulocyte colony-stimulating factors (GM-CSF
and G-CSF, respectively). Because erythroid burst- promoting activity (BPA)
is also elaborated by endothelial cells exposed to IL-1, we sought to
determine whether the BPA released by IL- 1-induced endothelial cells
simply reflects the known erythropoietic activity of GM-CSF or whether
other uncharacterized factors might be involved. Media conditioned by
multiply passaged endothelial cells cultured for three days with
recombinant IL-1 alpha (ECMIL-1) stimulated erythroid burst and GM colony
formation in cultures of human nonadherent T-lymphocyte-depleted marrow
mononuclear cells. Pretreatment with an anti-GM-CSF antiserum neutralized
all the BPA and 56% of the GM colony-stimulating activity (GM-CSA) in
ECMIL-1. The antiserum used in these studies did not inhibit IL-3 or G-CSF
activity and did not inhibit ECMIL-1-induced murine GM colony growth (a
measure of human G-CSF). To examine whether GM-CSF induces BPA release by
accessory cells, media conditioned by marrow cells cultured for three days
with GM-CSF were tested in the colony growth assays. Pretreatment with
anti-GM-CSF antiserum completely neutralized the BPA and GM-CSA of the
marrow cell-conditioned medium. We conclude that GM-CSF is the BPA
elaborated by IL-1-induced endothelial cells. The in vitro erythropoietic
activity of GM-CSF is not dependent on induced BPA release by accessory
cells and therefore likely results from a direct effect of GM-CSF on
progenitor cells.
Volume 72,
Issue 4,
pp. 1364-1367,
10/01/1988
Copyright © 1988 by The American Society of Hematology
