Neutrophil-Derived Microvesicle Induced Dysfunction of Brain Microvascular Endothelial Cells In Vitro
Abstract
:1. Introduction
2. Results
2.1. Characterization of NMV
2.2. NMV Are Internalised by Human Brain Endothelial Cells
2.3. The Internalization of NMV Occurs via Multiple Pathways
2.4. Internalization of NMV Impacts the Transcriptomic Profile of Brain Endothelial Cells
2.5. NMV Increase the Permeability and Decrease the Transendothelial Electrical Resistance of hCMEC/D3
3. Discussion
4. Materials and Methods
4.1. Cell Culture
4.2. Neutrophil-Derived Microvesicle Isolation
4.3. Flow Cytometric Analysis
4.4. Nanoparticle Tracking Analysis
4.5. Neutrophil Microvesicle Internalization by Endothelial Cells
4.6. Analysis of Internalization Pathways
4.7. RNA Extraction and Amplification
4.8. Microarray Amplification and Microarray Hybridization
4.9. Microarray Analysis
4.10. Permeability Assay
4.11. Transendothelial Electrical Resistance (TEER)
4.12. Statistical Analysis
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
AD | Alzheimer’s Disease |
BBB | Blood brain barrier |
BMEC | Brain microvascular endothelial cells |
CNS | Central nervous system |
EDTA | Ethylenediaminetetraacetic Acid |
EEA-1 | Early endosomal antigen-1 |
EIPA | 5-(N-Ethyl-N-isopropyl)amiloride |
fMLP | N-formylmethionine-leucyl-phenylalanine |
HCAEC | Human coronary arterial endothelial cells |
HUVEC | Human umbilical vein endothelial cells |
ICAM-1 | Intercellular adhesion molecule-1 |
LPS | Lipopolysachharide |
MDC | Monodansylcadaverine |
MFI | Mean Fluorescent Intensity |
MV | Microvesicles |
NMV | Neutrophil derived microvesicles |
NVU | Neuro vascular unit |
TEER | Tranendothelial electrical resistance |
TJ | Tight junction |
VaD | Vascular Dementia |
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Functional Group | p-Value | Number of Genes |
---|---|---|
Tight junction proteins | 0.0062 | 6 |
Vesicle mediated transport | 0.0074 | 19 |
Protein transport | 0.0019 | 18 |
RNA localization | 0.0011 | 9 |
Metal cluster binding | 0.032 | 4 |
FY-rich terminals | 0.0043 | 3 |
Pathway | p-Value |
---|---|
Ubiquitin-mediated proteolysis | 0.034 |
SNARE-mediated vesicular transport | 0.0163 |
P38 pathway/Regulation of SMAD2/3 signaling | 0.0191 |
Coenzyme B biosynthesis | 0.0209 |
Gap junction degradation | 0.0324 |
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Ajikumar, A.; Long, M.B.; Heath, P.R.; Wharton, S.B.; Ince, P.G.; Ridger, V.C.; Simpson, J.E. Neutrophil-Derived Microvesicle Induced Dysfunction of Brain Microvascular Endothelial Cells In Vitro. Int. J. Mol. Sci. 2019, 20, 5227. https://doi.org/10.3390/ijms20205227
Ajikumar A, Long MB, Heath PR, Wharton SB, Ince PG, Ridger VC, Simpson JE. Neutrophil-Derived Microvesicle Induced Dysfunction of Brain Microvascular Endothelial Cells In Vitro. International Journal of Molecular Sciences. 2019; 20(20):5227. https://doi.org/10.3390/ijms20205227
Chicago/Turabian StyleAjikumar, Anjana, Merete B. Long, Paul R. Heath, Stephen B. Wharton, Paul G. Ince, Victoria C. Ridger, and Julie E. Simpson. 2019. "Neutrophil-Derived Microvesicle Induced Dysfunction of Brain Microvascular Endothelial Cells In Vitro" International Journal of Molecular Sciences 20, no. 20: 5227. https://doi.org/10.3390/ijms20205227