Endothelial-Derived Extracellular Vesicles Induce Cerebrovascular Dysfunction in Inflammation
| Autor: | Mark C. Hirst, Ignacio A. Romero, Basil Sharrack, Cheryl A. Hawkes, Ruud D. Fontijn, Sarai Martinez-Pacheco, David Roig-Carles, David Male, Eduard Willms, Imre Mäger, Helga E. de Vries |
|---|---|
| Přispěvatelé: | Molecular cell biology and Immunology, Amsterdam Neuroscience - Neurovascular Disorders, ACS - Microcirculation, Amsterdam Neuroscience - Neuroinfection & -inflammation |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Chemistry
cell-to-cell communication Pharmaceutical Science Inflammation exosomes Blood–brain barrier blood–brain barrier Article Microvesicles neuroinflammation Endothelial stem cell Blot RS1-441 medicine.anatomical_structure Immune system Pharmacy and materia medica medicine Cancer research Tumor necrosis factor alpha medicine.symptom extracellular vesicles Neuroinflammation Uncategorized |
| Zdroj: | Pharmaceutics, Vol 13, Iss 1525, p 1525 (2021) Roig-Carles, D, Willms, E, Fontijn, R D, Martinez-Pacheco, S, Mäger, I, de Vries, H E, Hirst, M, Sharrack, B, Male, D K, Hawkes, C A & Romero, I A 2021, ' Endothelial-derived extracellular vesicles induce cerebrovascular dysfunction in inflammation ', Pharmaceutics, vol. 13, no. 9, 1525 . https://doi.org/10.3390/pharmaceutics13091525 Pharmaceutics Pharmaceutics, 13(9):1525. MDPI Multidisciplinary Digital Publishing Institute Volume 13 Issue 9 |
| ISSN: | 1999-4923 |
| DOI: | 10.3390/pharmaceutics13091525 |
| Popis: | Blood–brain barrier (BBB) dysfunction is a key hallmark in the pathology of many neuroinflammatory disorders. Extracellular vesicles (EVs) are lipid membrane-enclosed carriers of molecular cargo that are involved in cell-to-cell communication. Circulating endothelial EVs are increased in the plasma of patients with neurological disorders, and immune cell-derived EVs are known to modulate cerebrovascular functions. However, little is known about whether brain endothelial cell (BEC)-derived EVs themselves contribute to BBB dysfunction. Human cerebral microvascular cells (hCMEC/D3) were treated with TNFα and IFNy, and the EVs were isolated and characterised. The effect of EVs on BBB transendothelial resistance (TEER) and leukocyte adhesion in hCMEC/D3 cells was measured by electric substrate cell-substrate impedance sensing and the flow-based T-cell adhesion assay. EV-induced molecular changes in recipient hCMEC/D3 cells were analysed by RT-qPCR and Western blotting. A stimulation of naïve hCMEC/D3 cells with small EVs (sEVs) reduced the TEER and increased the shear-resistant T-cell adhesion. The levels of microRNA-155, VCAM1 and ICAM1 were increased in sEV-treated hCMEC/D3 cells. Blocking the expression of VCAM1, but not of ICAM1, prevented sEV-mediated T-cell adhesion to brain endothelia. These results suggest that sEVs derived from inflamed BECs promote cerebrovascular dysfunction. These findings may provide new insights into the mechanisms involving neuroinflammatory disorders. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|