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Endothelial Semaphorin 3F Maintains Endothelial Barrier Function and Inhibits Monocyte Migration

Einthoven Laboratory for Vascular and Regenerative Medicine, Department of Internal Medicine, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(4), 1471;
Received: 22 January 2020 / Revised: 17 February 2020 / Accepted: 18 February 2020 / Published: 21 February 2020
(This article belongs to the Special Issue Role of Neuronal Guidance Cues in Inflammation and Vascular Biology)
In normal physiology, endothelial cells (ECs) form a vital barrier between the blood and underlying tissue controlling leukocyte diapedesis and vascular inflammation. Emerging data suggest that neuronal guidance cues, typically expressed during development, have roles outside the nervous system in vascular biology and immune responses. In particular, Class III semaphorins have been reported to affect EC migration and angiogenesis. While ECs express high levels of semaphorin 3F (SEMA3F), little is known about its function in mature ECs. Here we show that SEMA3F expression is reduced by inflammatory stimuli and increased by laminar flow. Endothelial cells exposed to laminar flow secrete SEMA3F, which subsequently binds to heparan sulfates on the surface of ECs. However, under pro-inflammatory conditions, reduced levels of SEMA3F make ECs more prone to monocyte diapedesis and display impaired barrier function as measured with an electric cell–substrate impedance sensing system and a microfluidic system. In addition, we demonstrate that SEMA3F can directly inhibit the migration of activated monocytes. Taken together, our data suggest an important homeostatic function for EC-expressed SEMA3F, serving as a mediator of endothelial quiescence. View Full-Text
Keywords: semaphorin; endothelial cells; monocytes semaphorin; endothelial cells; monocytes
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MDPI and ACS Style

Zhang, H.; Vreeken, D.; Junaid, A.; Wang, G.; Sol, W.M.P.J.; de Bruin, R.G.; van Zonneveld, A.J.; van Gils, J.M. Endothelial Semaphorin 3F Maintains Endothelial Barrier Function and Inhibits Monocyte Migration. Int. J. Mol. Sci. 2020, 21, 1471.

AMA Style

Zhang H, Vreeken D, Junaid A, Wang G, Sol WMPJ, de Bruin RG, van Zonneveld AJ, van Gils JM. Endothelial Semaphorin 3F Maintains Endothelial Barrier Function and Inhibits Monocyte Migration. International Journal of Molecular Sciences. 2020; 21(4):1471.

Chicago/Turabian Style

Zhang, Huayu; Vreeken, Dianne; Junaid, Abidemi; Wang, Gangqi; Sol, Wendy M.P.J.; de Bruin, Ruben G.; van Zonneveld, Anton J.; van Gils, Janine M. 2020. "Endothelial Semaphorin 3F Maintains Endothelial Barrier Function and Inhibits Monocyte Migration" Int. J. Mol. Sci. 21, no. 4: 1471.

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