Inflammation-sensitive myosin-x functionally supports leukocyte extravasation by Cdc42-mediated ICAM-1-rich endothelial filopodia formation

Jeffrey Kroon, Antje Schaefer, Jos van Rijssel, Mark Hoogenboezem, Floris van Alphen, Peter Hordijk, Erik S. G. Stroes, Staffan Strömblad, Jacco van Rheenen, Jaap D. van Buul

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Leukocyte transendothelial migration is key to inflammation. Leukocytes first start rolling over the inflamed endothelium, followed by firmly adhering to it. Under inflammatory conditions, endothelial cells express small finger-like protrusions that stick out into the lumen. The function and regulation of these structures are unclear. We present evidence that these ICAM-1- and F-actin-rich endothelial finger-like protrusions are filopodia and function as adhesive structures for leukocytes to transit from rolling to crawling but are dispensable for diapedesis. Mechanistically, these structures require the motor function of myosin-X, activity of the small GTPase Cdc42, and p21-activated kinase 4. Moreover, myosin-X expression is under control of TNF-α-mediated c-Jun N-terminal kinase activity and is upregulated in human atherosclerotic regions. To our knowledge, this is the first study to identify that regulation of endothelial filopodia is crucial for leukocyte extravasation, in particular for the initiation of leukocyte adhesion under flow conditions.
Original languageEnglish
Pages (from-to)1790-1801
Number of pages12
JournalJournal of Immunology
Volume200
Issue number5
DOIs
Publication statusPublished - 2018

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