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Leeuwenhoek Centre for Advanced Microscopy, Section Molecular Cytology at Swammerdam Institute for Life Sciences at University of Amsterdam, Amsterdam, the Netherlands
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occurs in small capillaries, and subsequently transmigrate through the capillary wall, a process called extravasation ( 4 , 5 ). Cancer cells that have extravasated are frequently unable to survive, but may, in rare cases, form a micro-metastasis by
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Introduction The semi-permeable vascular barrier between the blood and the surrounding tissue is maintained by a monolayer of endothelial cells ( 1 ). The endothelial barrier regulates the extravasation of leukocytes and fluid ( 2 , 3
Leeuwenhoek Centre for Advanced Microscopy, Section Molecular Cytology at Swammerdam Institute for Life Sciences, the University of Amsterdam, Amsterdam, the Netherlands
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Department of Molecular Hematology, Sanquin Research, and Landsteiner Laboratory, Molecular Cell Biology Lab, Amsterdam, the Netherlands
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Leeuwenhoek Centre for Advanced Microscopy, Section Molecular Cytology at Swammerdam Institute for Life Sciences, the University of Amsterdam, Amsterdam, the Netherlands
Department of Molecular Hematology, Sanquin Research, and Landsteiner Laboratory, Molecular Cell Biology Lab, Amsterdam, the Netherlands
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capability of leukocytes to exit the vasculature at certain spots ( 9 ). Recently, research has demonstrated that leukocyte extravasation does not take place at random sites, on the endothelium, but at the so-called hotspot areas ( 10 , 11 , 12
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17 cells Effector CD4 + T cells specialized in fighting extracellular bacteria and fungi and involved in CNS autoimmunity. Their signature cytokine is IL-17 Extravasation of circulating immune cells across the vascular wall is a multi
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The endothelial barrier is a tightly regulated gateway in the transport of material between circulation and the tissues. Inflammatory mediators such as thrombin are able to open paracellular spaces in the endothelial monolayer to allow the extravasation of plasma proteins and leukocytes. Here we show that the protein SLIT-ROBO Rho GTPase-activating protein 2 (srGAP2) plays a critical role in regulating the extent of thrombin-mediated opening. We show that srGAP2 is not required for normal barrier function in resting endothelial cells, but that depletion of srGAP2 significantly increases the magnitude and duration of junctional opening in response to thrombin. We show that srGAP2 acts to switch off RhoA signaling after the contraction phase of thrombin-induced permeability, allowing respreading of cells and reformation of the barrier. srGAP2 is also required for effective restoration of the barrier after treatment with two other vasoactive agents that active RhoA – TNFα and angiotensin II. Taken together, we show that srGAP2 has a general function in controlling RhoA signaling in endothelial permeability, acting to limit the degree and duration of opening, by triggering the switch from endothelial cell contraction to respreading.
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an angiogenic response. Formation of gaps between pericytes in the pro-inflammatory environment of the infarct may be required for leukocyte extravasation. Pericytes also regulate microvascular function. Constriction of pericytes in the ischemic and
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). Disruption of ACE2 could exert additional detrimental effects in COVID-19 through undegraded DABK binding to the bradykinin B1 receptor (BKB1R). An excess DABK may contribute in causing microvascular leakage, leukocyte extravasation, and pulmonary oedema in
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extravasation towards the inflamed tissue. Different pathological conditions are characterized by important tissue inflammation, and ILs play a major role in all these inflammatory processes. An additional component of tissue inflammation is the presence of the
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Institute of Nuclear Sciences Applied to Health, University of Coimbra, Portugal
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Center for Developmental Biology and Regenerative Medicine, Seattle Children’s Research Institute, Seattle, Washington, USA
Department of Pediatrics, University of Washington, Seattle, Washington, USA
Department of Bioengineering, University of Washington, Seattle, Washington, USA
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. Embolus extravasation is an alternative mechanism for cerebral microvascular recanalization . Nature 2010 465 478 – 482 . ( https://doi.org/10.1038/nature09001 ) 11 Reeson P Choi K & Brown CE . VEGF signaling regulates the fate of obstructed
Wihuri Research Institute, Helsinki, Finland
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Wihuri Research Institute, Helsinki, Finland
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Beck H , Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions . Nature Medicine 2001 7 575 – 583 . ( https://doi.org/10
