TY  - JOUR
Y1  - 2020/01//
A1  - McCormack, JJ
A1  - Harrison-Lavoie, K
A1  - Cutler, DF
IS  - 1
AV  - public
JF  - Journal of Thrombosis and Haemostasis
EP  - 254
SN  - 1538-7836
N1  - This version is the author accepted manuscript . For information on re-use, please refer to the publisher?s terms and conditions.
ID  - discovery10082089
VL  - 18
N2  - BACKGROUND: The secretory granules of endothelial cells, Weibel-Palade bodies, are released in response to numerous extracellular signals. Their cargo is critical to many vascular functions including haemostasis and inflammation. This presents a fundamental problem; how can these cells initiate tailor-made responses from the release of a single type of organelle, each with similar cargo? Each cell contains Weibel-Palade bodies in a wide range of sizes, and we have shown that experimentally-shortening these organelles disproportionately reduces their ability to initiate haemostasis in vitro, leaving leukocyte recruitment unaffected. Could the production of this range of sizes underpin differential responses? OBJECTIVES: To determine whether different agonists drive the exocytosis of different sizes of Weibel-Palade bodies. METHODS: We used a high-throughput automated unbiased imaging workflow to analyse the sizes of Weibel-Palade bodies within HUVECs before and after agonist activation to determine changes in organelle size distributions. RESULTS: We found that a subset of agonists differentially evoke the release of the longest, most pro-haemostatic organelles. Inhibiting the release of these longest organelles by just 15% gives a fall of 60% in an assay of secreted VWF function. CONCLUSIONS: The size-selection of granules for exocytosis represents a novel layer of control, allowing endothelial cells to provide diverse responses to different signals via the release of a single type of organelle.
TI  - Human endothelial cells size-select their secretory granules for exocytosis to modulate their functional output
KW  - Endothelial Cells
KW  -  Exocytosis
KW  -  Organelle Size
KW  -  Weibel-Palade Bodies
KW  -  von Willebrand Factor
UR  - https://doi.org/10.1111/jth.14634
SP  - 243
ER  -