NR1 subunit of NMDA receptor regulates monocyte transmigration through the brain endothelial cell barrier

J. Neurochem. (2010) 113, 447-453. Normal neuronal functioning is dependent on the blood-brain barrier. This barrier is confined to specialized brain endothelial cells lining the inner vessel wall, and tightly controlling transport of nutrients, efflux of potentially harmful molecules and entry of i...

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Published in:Journal of neurochemistry 2010-04, Vol.113 (2), p.447-453
Main Authors: Reijerkerk, Arie, Kooij, Gijs, van der Pol, Susanne M.A, Leyen, Thomas, Lakeman, Kim, van het Hof, Bert, Vivien, Denis, de Vries, Helga E
Format: Article
Language:English
Subjects:
Animals
Autoimmune diseases
Biological and medical sciences
blood-brain barrier
Blood-Brain Barrier - drug effects
Blood-Brain Barrier - physiology
Brain
Brain - cytology
Cell Movement - drug effects
Cell Movement - physiology
Cells
Cells, Cultured
Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges
Chemokine CCL2 - metabolism
Disease Models, Animal
Dizocilpine Maleate - pharmacology
Encephalomyelitis, Autoimmune, Experimental - etiology
Encephalomyelitis, Autoimmune, Experimental - immunology
Encephalomyelitis, Autoimmune, Experimental - pathology
endothelial cell
Endothelial Cells - drug effects
Endothelial Cells - physiology
Enzyme Activation - drug effects
Excitatory Amino Acid Antagonists - pharmacology
Female
Fundamental and applied biological sciences. Psychology
Humans
Immunoprecipitation - methods
Leukocyte Common Antigens - metabolism
Medical sciences
Membrane Proteins - metabolism
Mice
monocyte
Monocytes - drug effects
Monocytes - physiology
Multiple sclerosis
Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis
Myelin Proteins
Myelin-Associated Glycoprotein - immunology
Myelin-Oligodendrocyte Glycoprotein
Neurology
Neurons
NMDA receptor
Phosphoproteins - metabolism
Receptors, N-Methyl-D-Aspartate - physiology
Signal Transduction - drug effects
Tissue Plasminogen Activator - pharmacology
tissue-type plasminogen activator
Vertebrates: nervous system and sense organs
Zonula Occludens-1 Protein
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Summary:J. Neurochem. (2010) 113, 447-453. Normal neuronal functioning is dependent on the blood-brain barrier. This barrier is confined to specialized brain endothelial cells lining the inner vessel wall, and tightly controlling transport of nutrients, efflux of potentially harmful molecules and entry of immune cells into the brain. Loss of blood-brain barrier function is an early and significant event which contributes to inflammation in the brain and subsequent progression of neuronal deficits in a number of brain disorders and has been well-documented for the auto-immune disease multiple sclerosis. Extravasation of cells happens by paracellular transport across the endothelial junctions, transcellularly across the endothelial cells, or both, and requires the active participation of endothelial cells. We and others have shown that this process requires the activity of proteases, including tissue-type plasminogen activator. We here describe a novel role for NMDA receptor, a potential cellular target of tissue-type plasminogen activator, in human brain endothelial cells. Our results show that the NMDA receptor subunit 1 (NR1) is expressed in brain endothelial cells, regulates tissue-type plasminogen activator-induced signal transduction and controls the passage of monocytes through the brain endothelial cell barrier. Together, our results hold significant promise for the treatment of chronic inflammation in the brain.
ISSN:0022-3042
1471-4159
DOI:10.1111/j.1471-4159.2010.06598.x