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Reactive oxygen intermediates induce regulated secretion of von Willebrand
factor from cultured human vascular endothelial cells
UM Vischer, L Jornot, CB Wollheim and JM Theler
Division de Biochimie Clinique, Centre Medical Universitaire, Geneva,
Switzerland.
Exocytosis from Weibel-Palade bodies, the secretory granules of vascular
endothelial cells, causes the rapid release of von Willebrand factor (vWF),
an adhesive glycoprotein involved in primary hemostasis, and cell surface
expression of P-selectin, a membrane protein involved in neutrophil
binding. Thus, exocytosis may represent a link between hemostasis and
inflammation. We investigated the effect of reactive oxygen intermediates
(ROIs) on vWF secretion. Incubation of cultured endothelial cells with
xanthine oxidase (XO), which generates superoxide anions (O2-), induces a
potent, rapid secretory response. However, vWF release was not observed in
response to H2O2. Extracellular, subendothelial vWF deposits typically seen
after exocytosis from Weibel-Palade bodies were observed after exposure to
XO. XO caused a rapid, sustained increase in intracellular free calcium
concentration ([Ca2+]i). vWF secretion was markedly inhibited by BAPTA- AM,
a cell-permeant calcium chelator. Removal of extracellular calcium did not
inhibit vWF release, although the sustained phase of the [Ca2+]i increase
was suppressed. These results suggest that XO-induced vWF release is
mediated by the initial increase in [Ca2+]i which is caused by calcium
mobilization from intracellular stores rather than by calcium influx.
Exocytosis from Weibel-Palade bodies may contribute to the pathogenic
effect of ROIs in atherosclerosis and inflammation.
Volume 85,
Issue 11,
pp. 3164-3172,
06/01/1995
Copyright © 1995 by The American Society of Hematology
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