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Differential regulation by cytokines of constitutive and stimulated
secretion of von Willebrand factor from endothelial cells
EM Paleolog, DC Crossman, JH McVey and JD Pearson
Section of Vascular Biology, MRC Clinical Research Centre, Harrow,
Middlesex, England.
We examined the effect of cytokines on basal and agonist-stimulated release
of von Willebrand factor (vWf) by human endothelial cells. Treatment of
endothelial cells for up to 48 hours with human recombinant or purified
interleukin 1 (IL-1) or human recombinant tumor necrosis factor-alpha
(TNF-alpha) did not significantly affect constitutive secretion of vWf or
intracellular levels of vWf, although basal prostacyclin (PGI2) production
was markedly enhanced. In contrast, both IL-1 and TNF-alpha modulated vWf
release in response to thrombin or phorbol ester. Pretreatment of
endothelial cells for 2 hours with either cytokine enhanced by up to
threefold the stimulatory effect of a subsequent 60-minute exposure to
thrombin. Addition of cycloheximide (5 micrograms/mL) during the
preincubation abolished this enhancement. Moreover, if the cytokine
pretreatment time was extended to 24 hours, agonist-stimulated vWf release
was significantly suppressed. Cytokine treatment for 2 or 24 hours had no
detectable effect on levels of vWf messenger RNA. The effects of cytokines
were not the result of contamination with bacterial lipopolysaccharide and
were not attributable to endothelial cell injury. These results show that
cytokines have little or no direct effect on vWf release from endothelial
cells but can significantly modulate its acute release in response to other
stimuli in a complex time- and dose-dependent manner.
Volume 75,
Issue 3,
pp. 688-695,
02/01/1990
Copyright © 1990 by The American Society of Hematology
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