Gamma-interferon modulates von Willebrand factor release by cultured human
endothelial cells
SH Tannenbaum and HR Gralnick
Clinical Pathology Department, National Institutes of Health, Bethesda, MD
20892.
Endothelial cells (EC) synthesize and secrete von Willebrand factor (vWF),
a multimeric glycoprotein required for normal hemostasis. Within human
endothelial cells, vWF multimers of extremely high molecular weight are
stored in rod-shaped organelles known as Weibel-Palade bodies. Inflammatory
mediators, such as interleukin-1, induce in vitro a variety of procoagulant
responses by EC, including the secretion of stored vWF. We postulated that
other inflammatory mediators might act to balance this procoagulant
reaction, thereby assisting in the maintenance of blood fluidity during
immune activation. Both gamma- interferon (gamma-IFN) and tumor necrosis
factor (TNF) were found to act independently and cooperatively to depress
the stimulated release of vWF from EC. Analysis of stored vWF in either
gamma-IFN and/or TNF- treated EC demonstrated a loss of high molecular
weight multimers while immunofluorescent studies documented a loss of
visible Weibel-Palade bodies. This suggests that gamma-IFN and TNF
interfere with normal vWF storage. gamma-IFN acted in a dose-, time-, and
RNA-dependent fashion, and its inhibition of vWF release was reversible
with time. No effect of gamma-IFN on EC was noted when anti-serum to
gamma-IFN was added. Unlike gamma-IFN, alpha-interferon did not effect EC
vWF. Therefore, gamma-IFN and TNF may be important in decreasing vWF
release during inflammatory or immunologic episodes.
Volume 75,
Issue 11,
pp. 2177-2184,
06/01/1990
Copyright © 1990 by The American Society of Hematology
