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A “lingering kiss” may reduce risk of blood clotting

08 February 2008

NIMR scientists have shown that the Weibel Palade body, an unusual secretory organelle found in the cells that line our blood vessels, can undergo a specialized form of exocytosis that allows selective release of small pro-inflammatory molecules, while retaining larger pro-coagulant molecules.

Weibel Palade bodies (WPBs), named after their discoverers the anatomist Ewald R. Weibel and the Nobel Prize winning cell biologist George E. Palade, are amongst the most unusual of secretory organelles in the animal kingdom (see Figure). Found exclusively within endothelial cells, the major core protein of the WPB is Von Willebrand factor (VWF) a large polymeric pro-coagulant molecule that plays a central role in primary and secondary haemostasis. Defects in or absence of this important protein leads to a wide range of blood clotting disorders. In recent years it has transpired that VWF is not alone within the WPB. An ever growing list of factors implicated in diverse processes such as blood vessel growth, bone remodelling and the regulation of inflammatory processes have been identified within the WPB. The inclusion of these molecules within WPB can change rapidly in response to pro- or anti-inflammatory signals and this remarkable plasticity has drawn a focus on the role of these secretory organelles in health and disease.

It has always been assumed that exocytosis of WPBs inevitably leads to secretion of VWF the major core protein. In a recent paper published in the journal Blood, scientists in NIMR's Division of Molecular Neuroendocrinology have shown that this is not always the case. By targeting different combinations of fluorescent cargo molecules into WPBs of living endothelial cells they were able to examine, in real time, the fates of these molecules during individual exocytotic events. Tom Carter (pictured), lead author of the paper, said:

these studies show that a population of WPBs can undergo a form of exocytosis, termed a lingering kiss, during which a small diameter (~12nm) long-lived fusion pore forms between the membrane of the WPB and the plasma membrane. This fusion pore behaves as a molecular filter allowing release of small pro-inflammatory molecules (such as the leukocyte chemo attractant IL-8), but not the much larger VWF.

The data show for the first time that the WPB can selectively release their cargo, a process that may allow the endothelial cell to regulate inflammatory processes with a reduced risk of thrombosis.

Weibel Palade bodies

Weibel Palade bodies; large rod-like secretory organelles unique to endothelial cells. An immunofluorescence image of a human endothelial cell labelled with specific antibodies against the major WPB core protein Von Willebrand factor (green in colour image) and the small eosinophil chemo attractant eotaxin-3 (red in merged image).