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Interferon-gamma upregulates interleukin-3 (IL-3) receptor expression in
human endothelial cells and synergizes with IL-3 in stimulating major
histocompatibility complex class II expression and cytokine production
EI Korpelainen, JR Gamble, WB Smith, M Dottore, MA Vadas and AF Lopez
Division of Human Immunology, Hanson Centre for Cancer Research, Adelaide,
South Australia.
The human interleukin-3 (IL-3) receptor is constitutively expressed on
certain hematopoietic cells where it mediates proliferation and
differentiation, or functional activation. We have recently found that
human umbilical vein endothelial cells (HUVECs) also express IL-3 receptors
and that the expression is enhanced by stimulation with the monokine tumor
necrosis factor alpha. In this report we show that the lymphokine
interferon gamma (IFN gamma) is a powerful stimulator of the IL-3 receptor
of HUVECs and that the combination of IL-3 and IFN gamma has a synergistic
effect on major histocompatibility complex (MHC) class II expression and on
the production of the early-acting hematopoietic cytokines IL-6 and
granulocyte colony-stimulating factor (G-CSF). IFN gamma caused a time- and
dose-dependent up-regulation of mRNA for both the alpha and beta chains of
the IL-3 receptor, with maximal effects occurring 12 to 24 hours after
stimulation with IFN gamma at 100 U/mL. Induction of mRNA correlated with
protein expression on the cell surface, as judged by monoclonal antibody
staining of both receptor chains and by the ability of HUVEC to
specifically bind 125I- labeled IL-3 (125I-IL-3). Scatchard analysis of
HUVECs stimulated with IFN gamma at 100 U/mL for 24 hours showed
approximately 6,300 IL-3 receptors per cell that were of a high affinity
class (dissociation constant [kd] = 500 pmol/L) only. The addition of IL-3
to IFN gamma- treated HUVECs strongly enhanced the expression of MHC class
II antigen. Importantly, IFN gamma and IL-3 also exhibited a synergistic
effect in the induction of the mRNA for G-CSF and IL-6. This was reflected
in increased amounts of G-CSF and IL-6 protein in HUVEC supernatants. In
contrast, IFN gamma and IL-3 did not stimulate granulocyte-macrophage
colony-stimulating factor (GM-CSF) or IL-8 production in HUVECs. These
results show that IFN gamma is a strong stimulator of IL-3 receptor
expression in HUVECs and suggest that in vivo T-cell activation, causing
the concomitant production of IFN gamma and IL-3, may lead to enhanced
endothelial MHC class II expression and to the selective production of
early-acting hematopoietic cytokines. Thus, IL-3 could influence immunity
and hematopoiesis by acting not only on hematopoietic cells, but also on
vascular endothelium.
Volume 86,
Issue 1,
pp. 176-182,
07/01/1995
Copyright © 1995 by The American Society of Hematology
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