TY - JOUR
T1 - Inflammation-sensitive myosin-x functionally supports leukocyte extravasation by Cdc42-mediated ICAM-1-rich endothelial filopodia formation
AU - Kroon, Jeffrey
AU - Schaefer, Antje
AU - van Rijssel, Jos
AU - Hoogenboezem, Mark
AU - van Alphen, Floris
AU - Hordijk, Peter
AU - Stroes, Erik S. G.
AU - Strömblad, Staffan
AU - van Rheenen, Jacco
AU - van Buul, Jaap D.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85044757309&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29386254
U2 - https://doi.org/10.4049/jimmunol.1700702
DO - https://doi.org/10.4049/jimmunol.1700702
M3 - Article
C2 - 29386254
SN - 0022-1767
VL - 200
SP - 1790
EP - 1801
JO - Journal of Immunology
JF - Journal of Immunology
IS - 5
ER -