Basal secretion of von Willebrand factor from human endothelial cells

被引:100
作者
Giblin, Jonathan P. [1 ]
Hewlett, Lindsay J. [1 ]
Hannah, Matthew J. [1 ]
机构
[1] Natl Inst Med Res, MRC, Dept Mol Neuroendocrinol, London NW7 1AA, England
基金
英国医学研究理事会;
关键词
D O I
10.1182/blood-2007-12-130740
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Endothelial cells store the adhesive glycoprotein von Willebrand factor (VWF) in Weibel-Palade bodies (WPBs), distinctively shaped regulated secretory organelles that undergo exocytosis in response to secretagogue. A significant proportion of newly synthesized VWF is also secreted spontaneously from nonstimulated cells, through what is thought to be the constitutive secretory pathway. To learn more about VWF trafficking, we performed kinetic analyses of the storage and nonstimulated secretion of VWF in cultured human endothelial cells. We found that most VWF was secreted through a route that was significantly delayed compared with constitutive secretion, although this pathway was responsible for secretion of a small amount of uncleaved VWF precursor. Disruption of pH-dependent sorting processes with ammonium chloride converted the secretion kinetics of mature VWF to that of its precursor. Conversely, preventing constitutive secretion of nascent protein with brefeldin A had only a modest effect on the spontaneous release of VWF, showing that most VWF secreted by nonstimulated cells was not constitutive secretion but basal release of a post-Golgi storage organelle, presumably the WPB. These data suggest that VWF is sorted to the regulated secretory pathway in endothelial cells much more efficiently than previously reported.
引用
收藏
页码:957 / 964
页数:8
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