MRC National Institute for Medical Research, London
Science for Health
Secretion from Weibel-Palade bodies
26 March 2009
Weibel-Palade bodies (WPBs) are secretory organelles found in the cells that line our blood vessels, called endothelial cells. WPBs secrete proteins that play important roles in regulating inflammatory and haemostatic responses. Inflammation is associated with the extracellular acidification of tissues and blood, conditions that can alter the behaviour of secreted proteins.
Tom Carter (pictured), from NIMR's Division of Molecular Neuroendocrinology, working with Matthew Hannah in the same Division, investigated what effect extracellular pH has on the release of a wide range of soluble and membrane proteins from WPBs, including the pro-coagulant molecule von Willebrand factor (VWF). His team used biochemical approaches and direct optical analysis of individual WPB fusion events in human endothelial cells expressing green or red fluorescent fusions of VWF and other secreted proteins.
They found that extracellular acidification to levels of pH 6.8 or lower altered the behaviour of secreted von Willebrand factor in such a way as to make it less likely to promote blood clotting. In contrast the release of a range of the small pro-inflammatory mediators was essentially unaltered. Together these data show that the external environment can have a profound influence on how the different secreted proteins behave once released.
Dr Carter said:
Weibel-Palade bodies contain a wide range of proteins that control different biological processes. Our data shows that the external environment can alter the behaviour of these different secreted proteins. In doing so it may help fine-tune the functional consequences of the secretory response to match local requirements, e.g. to allow the release of molecules to control inflammatory processes while limiting the risk of blood clotting.
Original article
The research findings are published in full in:
Babich V, Knipe L, Hewlett L, Meli A, Dempster J, Hannah MJ, Carter T. (2009)
Differential effect of extracellular acidosis on the release and dispersal of soluble and membrane proteins secreted from the Weibel-Palade body
Journal of Biological Chemistry Epub ahead of print. Publisher abstract
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