Human Brain Microvascular Endothelial Cells and Umbilical Vein Endothelial Cells Differentially Facilitate Leukocyte Recruitment and Utilize Chemokines for T Cell Migration

Man, Shumei; Ubogu, Eroboghene E.; Williams, Katherine; Tucky, Barbara; Callahan, Melissa K.; Ransohoff, Richard M.

doi:10.1155/2008/384982

Cited by 85 publications

(80 citation statements)

References 38 publications

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“…In vitro studies using human cells therefore represent a useful alternative approach, yet most studies of cerebrovascular function use monotypic cultures of brain ECs, which do not mimic the complexity of cell-cell and/or cell-matrix interactions found in the native vessel. As an improvement, EC and astrocytes, EC and SMC, and EC and pericytes have been co-cultured, however, this is almost always under static culture conditions (Di et al, 2009;Cho et al, 2007;Bicker et al, 2014;Navone et al, 2013;Man et al, 2008;Hatherell et al, 2011;Bussolari et al, 1982;Cucullo et al, 2007). More recent studies developed an EC and astrocyte co-culture model using a complex flow system, but this model did not allow histological analysis or cell-ECM interactions to be assessed (Cucullo et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

[O2–04–01]: Clearance of Beta‐amyloid Is Facilitated by Apolipoprotein E and Circulating High‐density Lipoproteins in Bioengineered Human Vessels

Robert

Button

Soo

et al. 2017

Alzheimer's & Dementia

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Amyloid plaques, consisting of deposited beta-amyloid (Ab), are a neuropathological hallmark of Alzheimer's Disease (AD). Cerebral vessels play a major role in AD, as Ab is cleared from the brain by pathways involving the cerebrovasculature, most AD patients have cerebrovascular amyloid (cerebral amyloid angiopathy (CAA), and cardiovascular risk factors increase dementia risk. Here we present a notable advance in vascular tissue engineering by generating the first functional 3-dimensioinal model of CAA in bioengineered human vessels. We show that lipoproteins including brain (apoE) and circulating (high-density lipoprotein, HDL) synergize to facilitate Ab transport across bioengineered human cerebral vessels. These lipoproteins facilitate Ab42 transport more efficiently than Ab40, consistent with Ab40 being the primary species that accumulates in CAA. Moreover, apoE4 is less effective than apoE2 in promoting Ab transport, also consistent with the well-established role of apoE4 in Ab deposition in AD.

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Section: Discussionmentioning

confidence: 99%

[O2–04–01]: Clearance of Beta‐amyloid Is Facilitated by Apolipoprotein E and Circulating High‐density Lipoproteins in Bioengineered Human Vessels

Robert

Button

Soo

et al. 2017

Alzheimer's & Dementia

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“…However, we show that platelet-secreted IL-1␣ is capable of driving endothelial activation, whereas CD40L-mediated endothelial activation is thought to be dependent on direct platelet-endothelial cell-cell contact. 20,45 Given the unique characteristics of brain endothelial expression of, and response to, inflammatory mediators, [47][48][49] further studies are required to determine whether and how platelet CD40L influences brain endothelial inflammation.…”

Section: Discussionmentioning

confidence: 99%

Platelet interleukin-1α drives cerebrovascular inflammation

Thornton

McColl

Greenhalgh

et al. 2010

Blood

153

133

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IntroductionCerebrovascular inflammation is a major contributor to diverse forms of brain injury, including cerebral ischemia, multiple sclerosis, cerebral infection, and epilepsy. 1-3 Peripheral circulating cells play critical roles in cerebral inflammation. Platelets are one of the first cell types to arrive at the site of vascular dysfunction 4 and can induce vascular inflammation, thus contributing to disease progression, particularly in larger vessels.The effects of platelets on microvascular endothelial cells are poorly understood, although interactions between these cellular entities are documented in the brain in response to cerebral ischemia in several species 5-9 and in cerebral malaria in humans. 10 Platelet activation occurs in response to stroke in humans 11,12 and in patients with multiple sclerosis. 13 Platelet consumption or brain accumulation 14 in the infarct area may account for the drop in platelet numbers after clinical stroke. 15 Inhibition of platelet adhesion to brain endothelium may protect against diverse brain insults. Neutralizing platelet glycoprotein (GP) VI or GPIb surface adhesion receptors reduces damage in mouse focal cerebral ischemia. 16 Inhibition of platelet-brain endothelial interactions, through blockade of platelet GPIIb receptor, protects mice against cerebral malaria pathogenesis. 17 Mice lacking platelet GPIIb 18 or mice receiving a small molecule inhibitor of GPIIb/IIIa (CD41/CD61) are also protected against cerebral ischemia. 5 However, the mechanisms by which platelets contribute to brain injury are unknown.Current therapies for the treatment of acute cerebral ischemia target platelet function, with protective effects dependent on anticoagulant or fibrinolytic actions. However, inhibition of coagulatory pathways reduces inflammation. 19 Thus, the antiinflammatory effects of platelet inhibition may mediate some of the protection afforded by these therapies in cerebral ischemia. Platelet interleukin-1␣ (IL-1␣), IL-1␤, or CD40L can activate peripheral endothelial cells, [20][21][22][23][24] and platelets contribute to leukocyte infiltration in peripheral tissues. 25,26 Similar mechanisms may contribute to brain endothelial activation.Here, we tested the hypothesis that platelets induce inflammatory activation of brain endothelial cells. We show, for the first time, that platelet-secreted IL-1␣ drives mouse brain endothelial activation, leading to the induction of endothelial ICAM-1 and VCAM-1, CXCL1 release, and neutrophil transendothelial migration (TEM). This study is the first to show that actions of platelet IL-1␣ on brain endothelium may be critical to inflammationmediated injury in the brain. MethodsMore details regarding the procedures outlined herein are given in supplemental Methods (available on the Blood Web site; see the Supplemental Materials link at the top of the online article). Focal cerebral ischemia and immunohistochemistryFocal cerebral ischemia in C57/BL6 or IL-1␣/␤ Ϫ/Ϫ mice (on a C57/BL6 background 27 ) induced by transient (60 minutes) middle cer...

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“…It forms a polarized monolayer during confluence with characteristics similar to the primary human brain MEC. This human cell line is commonly used to study BBB function and permeability [11, 12]. THBMEC was propagated using M199 medium supplemented with 5% heat-inactivated fetal bovine serum (FBS) and 1% penicillin/streptomycin antibiotics.…”

Section: Methodsmentioning

confidence: 99%

Loss of Transfected Human Brain Micro-Vascular Endothelial Cell Integrity during Herpes Simplex Virus Infection

et al. 2018

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Objective: Herpes simplex virus infection through the neuronal route is the most well-studied mode of viral encephalitis that can persists in a human host for a lifetime. However, the involvement of other possible infection mechanisms by the virus remains underexplored. Therefore, this study aims to determine the temporal effects and mechanisms by which the virus breaches the human brain micro-vascular endothelial cells of the blood-brain barrier. Method: An electrical cell-substrate impedance-sensing tool was utilized to study the real-time cell-cell barrier or morphological changes in response to the virus infection. Results: Herpes simplex virus, regardless of type (i.e., 1 or 2), reduced the cell-cell barrier resistance almost immediately after virus addition to endothelial cells, with negligible involvement of cell-matrix adhesion changes. There is no exclusivity in the infection ability of endothelial cells. From 30 h after HSV infection, there was an increase in cell membrane capacitance with a subsequent loss of cell-matrix adhesion capability, indicating a viability loss of the infected endothelial cells. Conclusion: This study shows for the first time that destruction of human brain micro-vascular endothelial cells as an in vitro model of the blood-brain barrier could be an alternative invasion mechanism during herpes simplex virus infection.

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Human Brain Microvascular Endothelial Cells and Umbilical Vein Endothelial Cells Differentially Facilitate Leukocyte Recruitment and Utilize Chemokines for T Cell Migration

Cited by 85 publications

References 38 publications

[O2–04–01]: Clearance of Beta‐amyloid Is Facilitated by Apolipoprotein E and Circulating High‐density Lipoproteins in Bioengineered Human Vessels

[O2–04–01]: Clearance of Beta‐amyloid Is Facilitated by Apolipoprotein E and Circulating High‐density Lipoproteins in Bioengineered Human Vessels

Platelet interleukin-1α drives cerebrovascular inflammation

Loss of Transfected Human Brain Micro-Vascular Endothelial Cell Integrity during Herpes Simplex Virus Infection

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