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  Mechanosensation by endothelial PIEZO1 is required for leukocyte diapedesis.

Wang, S., Wang, B., Shi, Y., Moller, T., Stegmeyer, R. I., Strilic, B., et al. (2022). Mechanosensation by endothelial PIEZO1 is required for leukocyte diapedesis. Blood. doi:10.1182/blood.2021014614.

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 Creators:
Wang, ShengPeng1, Author              
Wang, Bianbian, Author
Shi, Yue, Author
Moller, Tanja, Author
Stegmeyer, Rebekka I, Author
Strilic, Boris1, Author              
Li, Ting, Author
Yuan, Zuyi, Author
Wang, Changhe, Author
Wettschureck, Nina1, Author              
Vestweber, Dietmar, Author
Offermanns, Stefan1, Author              
Affiliations:
1Pharmacology, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591696              

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 Abstract: The extravasation of leukocytes is a critical step during inflammation which requires the localized opening of the endothelial barrier. This process is initiated by the close interaction of leukocytes with various adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) on the surface of endothelial cells. Here we reveal that mechanical forces generated by leukocyte-induced clustering of ICAM-1 synergistically with fluid shear stress exerted by the flowing blood increase endothelial plasma membrane tension to activate the mechanosensitive cation channel PIEZO1. This leads to increases in [Ca2+]i and activation of downstream signaling events including phosphorylation of SRC, PYK2 and myosin light chain resulting in opening of the endothelial barrier. Mice with endothelium-specific Piezo1 deficiency show decreased leukocyte extravasation in different inflammation models. Thus, leukocytes and the hemodynamic microenvironment synergize to mechanically activate endothelial PIEZO1 and subsequent downstream signaling to initiate leukocyte diapedesis. Copyright © 2022 American Society of Hematology.

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 Dates: 2022-04-202022
 Publication Status: Published in print
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 Identifiers: ISI: 35443048
DOI: 10.1182/blood.2021014614
PMID: 35443048
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Title: Blood
Source Genre: Journal
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Pages: - Volume / Issue: - Sequence Number: - Start / End Page: - Identifier: ISSN: 1528-0020