Endothelial Semaphorin 3F Maintains Endothelial Barrier Function and Inhibits Monocyte Migration.
Huayu ZhangDianne VreekenAbidemi JunaidGangqi WangWendy M P J SolRuben G de BruinAnton Jan van ZonneveldJanine M van GilsPublished in: International journal of molecular sciences (2020)
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.
Keyphrases
- endothelial cells
- high glucose
- vascular endothelial growth factor
- immune response
- dendritic cells
- oxidative stress
- single cell
- electronic health record
- poor prognosis
- peripheral blood
- big data
- magnetic resonance imaging
- stem cells
- high throughput
- artificial intelligence
- cell therapy
- binding protein
- blood brain barrier
- data analysis
- bone marrow
- wound healing
- contrast enhanced