Inflammation-induced brain endothelial activation leads to uptake of electrostatically stabilized iron oxide nanoparticles via sulfated glycosaminoglycans.

Autor: Berndt D; Institute for Medical Immunology, Charité-Universtitätsmedizin Berlin, Berlin, Germany; Cluster of Excellence NeuroCure and Department of Neurology and Experimental and Clinical Research Center, Universitätsmedizin Berlin, Berlin, Germany., Millward JM; Institute for Medical Immunology, Charité-Universtitätsmedizin Berlin, Berlin, Germany; Experimental and clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité Universitätsmedizin, Berlin., Schnorr J; Department of Radiology, Charité-Universitätsmedizin Berlin, Berlin, Germany., Taupitz M; Department of Radiology, Charité-Universitätsmedizin Berlin, Berlin, Germany., Stangl V; Medizinische Klinik mit Schwerpunkt Kardiologie und Angiologie, Charité, Universitätsmedizin Berlin, Berlin, Germany., Paul F; Experimental and clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité Universitätsmedizin, Berlin; Cluster of Excellence NeuroCure and Department of Neurology and Experimental and Clinical Research Center, Universitätsmedizin Berlin, Berlin, Germany., Wagner S; Department of Radiology, Charité-Universitätsmedizin Berlin, Berlin, Germany., Wuerfel JT; Cluster of Excellence NeuroCure and Department of Neurology and Experimental and Clinical Research Center, Universitätsmedizin Berlin, Berlin, Germany., Sack I; Department of Radiology, Charité-Universitätsmedizin Berlin, Berlin, Germany., Ludwig A; Medizinische Klinik mit Schwerpunkt Kardiologie und Angiologie, Charité, Universitätsmedizin Berlin, Berlin, Germany., Infante-Duarte C; Institute for Medical Immunology, Charité-Universtitätsmedizin Berlin, Berlin, Germany; Experimental and clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité Universitätsmedizin, Berlin. Electronic address: carmen.infante@charite.de.
Jazyk: angličtina
Zdroj: Nanomedicine : nanotechnology, biology, and medicine [Nanomedicine] 2017 May; Vol. 13 (4), pp. 1411-1421. Date of Electronic Publication: 2017 Jan 25.
DOI: 10.1016/j.nano.2017.01.010
Abstrakt: Based on our previous data on the presence of very small superparamagnetic iron oxide nanoparticles (VSOP) on brain endothelial structures during experimental autoimmune encephalomyelitis (EAE), we investigated the mechanisms of VSOP binding on inflamed brain endothelial cells in vivo and in vitro. After intravenous application, VSOP were detected in brain endothelial cells of EAE animals at peak disease and prior to clinical onset. In vitro, inflammatory stimuli increased VSOP uptake by brain endothelial bEnd.3 cells, which we confirmed in primary endothelial cells and in bEnd.3 cells cultured under shear stress. Transmission electron microscopy and blocking experiments revealed that during inflammation VSOP were endocytosed by bEnd.3. Modified sulfated glycosaminoglycans (GAG) on inflamed brain endothelial cells were the primary binding site for VSOP, as GAG degradation and inhibition of GAG sulfation reduced VSOP uptake. Thus, VSOP-based MRI is sensitive to visualize early neuroinflammatory processes such as GAG modifications on brain endothelial cells.
(Copyright © 2017 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: