title: GM-CSF promotes migration of human monocytes across the blood brain barrier.
abstract: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Infiltration of monocytes into the CNS is crucial for disease onset and progression. Animal studies indicate that granulocyte-macrophages colony-stimulating factor (GM-CSF) may play an essential role in this process, possibly by acting on the migratory capacities of myeloid cells across the blood-brain barrier. This study describes the effect of GM-CSF on human monocytes, macrophages, and microglia. Furthermore, the expression of GM-CSF and its receptor was investigated in the CNS under healthy and pathological conditions. We show that GM-CSF enhances monocyte migration across human blood-brain barrier endothelial cells in vitro. Next, immunohistochemical analysis on human brain tissues revealed that GM-CSF is highly expressed by microglia and macrophages in MS lesions. The GM-CSF receptor is expressed by neurons in the rim of combined gray/white matter lesions and astrocytes. Finally, the effect of GM-CSF on human macrophages was determined, revealing an intermediate activation status, with a phenotype similar to that observed in active MS lesions. Together our data indicate that GM-CSF is a powerful stimulator of monocyte migration, and is abundantly present in the inflamed CNS where it may act as an activator of macrophages and microglia.
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center Amsterdam, Neuroscience Campus, Amsterdam, The Netherlands.|Department of Pathology, VU University Medical Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: Daphne Y S
authors.initials: DY
authors.lastname: Vogel
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center Amsterdam, Neuroscience Campus, Amsterdam, The Netherlands.
authors.forename: Gijs
authors.initials: G
authors.lastname: Kooij
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center Amsterdam, Neuroscience Campus, Amsterdam, The Netherlands.
authors.forename: Priscilla D A M
authors.initials: PD
authors.lastname: Heijnen
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center Amsterdam, Neuroscience Campus, Amsterdam, The Netherlands.
authors.forename: Marjolein
authors.initials: M
authors.lastname: Breur
authors.affiliation: Department of Pathology, VU University Medical Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: Laura A N
authors.initials: LA
authors.lastname: Peferoen
authors.affiliation: Department of Pathology, VU University Medical Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: van der Valk
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center Amsterdam, Neuroscience Campus, Amsterdam, The Netherlands.
authors.forename: Helga E
authors.initials: HE
authors.lastname: de Vries
authors.affiliation: Department of Pathology, VU University Medical Center Amsterdam, Amsterdam, The Netherlands.|Department of Neuroimmunology Unit, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, UK.
authors.forename: Sandra
authors.initials: S
authors.lastname: Amor
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center Amsterdam, Neuroscience Campus, Amsterdam, The Netherlands.
authors.forename: Christine D
authors.initials: CD
authors.lastname: Dijkstra
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells; D005260:Female; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D057705:Transendothelial and Transepithelial Migration / Q000187:drug effects / Q000276:immunology*
chemical_list: D016207:Cytokines; D017382:Reactive Oxygen Species; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: CNS; MS; Migration; Monocytes; macrophages