Altered vascular permeability and early onset of experimental autoimmune encephalomyelitis in PECAM-1–deficient mice

Graesser, Donnasue; Solowiej, Anna; Bruckner, Monika; Osterweil, Emily K.; Juedes, Amy E.; Davis, Sandra; Ruddle, Nancy H.; Engelhardt, Britta; Madri, Joseph A.

doi:10.1172/jci200213595

Cited by 128 publications

(180 citation statements)

References 41 publications

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“…These results are consistent with literature-described data that showed in vivo expression of these CAMs on mouse CNS microvessels (PECAM-1, 44 ICAM-1, 45 ICAM-2 46 and VCAM-1 47,48 ). Expression of these molecules was compared to MAdCAM-1 expression as negative control.…”

Section: Discussionsupporting

confidence: 93%

Mouse syngenic in vitro blood–brain barrier model: a new tool to examine inflammatory events in cerebral endothelium

Coisne

Dehouck

Faveeuw

et al. 2005

Laboratory Investigation

165

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Although cerebral endothelium disturbance is commonly observed in central nervous system (CNS) inflammatory pathologies, neither the cause of this phenomenon nor the effective participation of bloodbrain barrier (BBB) in such diseases are well established. Observations were mostly made in vivo using mouse models of chronic inflammation. This paper presents a new mouse in vitro model suitable for the study of underlying mechanistic events touching BBB functions during CNS inflammatory disturbances. This model consists of a coculture with both primary cell types isolated from mice. Mouse brain capillary endothelial cell (MBCEC)s coming from brain capillaries are in culture with their in vivo partners and form differentiated monolayers that retain endothelial markers and numerous phenotypic properties of in vivo cerebral endothelium, such as: (1) Keywords: BBB; in vitro model; coculture; tight junction; P-glycoprotein; cell adhesion moleculeThe maintenance of brain interstitial fluid homeostasis is established by the presence of the bloodbrain barrier (BBB) which can be considered as the main interface between blood and brain parenchymal cells. This endothelium can be distinguished from the other vascular beds by the presence of continuous tight junctions and the absence of fenestration or channel. Both of these characteristics reduce the unspecific transport of molecules across the BBB. The blood/brain exchanges involve specific carrier-mediated transport systems that facilitate the uptake of nutrients. 1,2 BBB damage commonly associated to inflammatory events has been reported in several central nervous system (CNS) infections and neurodegenerative diseases. [3][4][5] Although BBB permeability disturbances seem to be critical steps as they lead to brain damage, neither the cause of these phenomena nor the effective participation of BBB in such diseases are established.The cerebral vascular wall was formally considered as a barrier that isolates brain from immunecontrol. However, the presence of immune cells in the brain parenchyma in healthy animals, and their increased cerebral residence in pathogenic conditions, demonstrate that the recruitment of inflammatory cells into the CNS, through the BBB, takes place. 6,7 In fact, the presence of cell adhesion molecules (CAMs) on the BBB suggests a direct and selective interaction between blood cells and the cerebral endothelium. These molecules, first described in peripheral capillaries, may mediate leukocyte transmigration across the BBB in a multistep process. 8,9 BBB damages and leukocyte infiltration in brain parenchyma were mostly examined using in vivo mouse models of chronic inflammation, which are

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Section: Discussionsupporting

confidence: 93%

Mouse syngenic in vitro blood–brain barrier model: a new tool to examine inflammatory events in cerebral endothelium

Coisne

Dehouck

Faveeuw

et al. 2005

Laboratory Investigation

165

View full text Add to dashboard Cite

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“…Besides, PECAM modulates the level of β-catenin by controlling glycogene synthase kinase β (GSKβ) activity and the rate of β-catenin degradation [Biswas et al, 2006]. Indeed, PECAM-1-null mice exhibit prolonged and increased permeability after inflammatory insults, proving unequivocally that PECAM plays positive role in maintaining barrier function [Graesser et al, 2002]. Recent study showed that due to it endothelial localization and properties, PECAM may serve as a target for an endothelial drug delivery.…”

Section: Adhesion Complexes and Increased Transendothelial Permeabilitymentioning

confidence: 99%

The role of cytoskeleton in the regulation of vascular endothelial barrier function

Bogatcheva

Verin

2008

Microvascular Research

167

143

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The cytoskeleton is vital to the function of virtually all cell types in the organism as it is required for cell division, cell motility, endo-or exocytosis and the maintenance of cell shape. Endothelial cells, lining the inner surface of the blood vessels, exploit cytoskeletal elements to ensure the integrity of cell monolayer in quiescent endothelium, and to enable the disintegration of the formed barrier in response to various agonists. Vascular permeability is defined by the combination of transcellular and paracellular pathways, with the latter being a major contributor to the inflammation-induced barrier dysfunction. This review will analyze the cytoskeletal elements, which reorganization affects endothelial permeability, and emphasize signaling mechanisms with barrier-protective or barrierdisruptive potential.

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“…25 Down-regulation of PECAM-1 is associated with defective vascular permeability in an animal model. 26 PECAM-1 is also associated with cadherin and several cytoplasmic proteins to modulate intercellular transport, 27 and with extracellular matrix-binding protein to control adhesive and migratory cellular activities. [28][29][30] Our present study has demonstrated effects of CHH on expression levels of junctional proteins and their function in vascular endothelial EA.hy926 cells.…”

Section: Resultsmentioning

confidence: 99%

Hypobaric hypoxia down-regulated junctional protein complex: Implications to vascular leakage

Souvannakitti

Peerapen

Thongboonkerd

2016

Cell Adhesion & Migration

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Acute mountain sickness (AMS) can cause capillary hyper-permeability and vasogenic edema. However, its underlying mechanisms remained unclear and there is no previous in vitro study on AMS. We therefore conducted an in vitro study and examined whether continuous hypobaric hypoxia (CHH) could alter expression of junctional protein complex of vascular endothelial cells, causing hyper-permeabilization. EA.hy926 human endothelial cells were exposed to either CHH or normoxia for up to 24 h. Flow cytometry using annexin V/propidium iodide co-staining demonstrated that cell death had no significant difference at 12-h, but was increased by CHH at 24-h. Transendothelial resistance (TER) of endothelial cell monolayer was progressively decreased by CHH from 1-h to 24-h. Western blot analysis and immunofluorescence study demonstrated decreased expression levels of VE-cadherin, PECAM-1 and ZO-1 junctional proteins at both 12-h and 24-h exposure time-points. Interestingly, while the main form of ZO-1 (220 kDa) was decreased, its degraded form (100 kDa) was increased by 24-h CHH that might be linked to the increased cell death. Our data have demonstrated that CHH caused vascular endothelial hyper-permeability and defective junctional protein complex by reducing expression levels of VE-cadherin, PECAM-1, and ZO-1. Taken together, these data may explain pathophysiology underlying vascular hyperpermeability in AMS.

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Altered vascular permeability and early onset of experimental autoimmune encephalomyelitis in PECAM-1–deficient mice

Cited by 128 publications

References 41 publications

Mouse syngenic in vitro blood–brain barrier model: a new tool to examine inflammatory events in cerebral endothelium

Mouse syngenic in vitro blood–brain barrier model: a new tool to examine inflammatory events in cerebral endothelium

The role of cytoskeleton in the regulation of vascular endothelial barrier function

Hypobaric hypoxia down-regulated junctional protein complex: Implications to vascular leakage

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