Cited by 94Multiple Sclerosis Research StudiesNeuroinflammation and Neurodegeneration MechanismsBarrier Structure and Function Studies

GM‐CSF promotes migration of human monocytes across the blood brain barrier

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Vogel, Daphne Y. S., Kooij, Gijs, Heijnen, Priscilla D. A. M., Breur, Marjolein, Peferoen, Laura A. N., van der Valk, Paul, de Vries, Helga E., Amor, Sandra +1 more·2015·European Journal of Immunology

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.

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  • CSF-2 promotes migration of blood-borne monocytes across the blood-brain barrier, which then differentiate into macrophages in the presence of CSF-1 and CSF-2.

    “CSF-2 promotes migration of blood-borne monocytes across the blood-brain barrier, which then differentiate into macrophages in the presence of CSF-1 and CSF-2 [16, 17, 26, 52].”

    From Loss of homeostatic microglial phenotype in CSF1R-related Leukoencephalopathy (2020) · cites this paper as [52]

    The Discussion reports that GM-CSF (CSF-2) increased human monocyte migration across a blood-brain-barrier endothelial layer in vitro, and says monocytes mature into macrophages after entering the CNS. The Introduction and Human macrophages methods describe GM-CSF-associated maturation and macrophage culture, but do not establish that the migrated monocytes subsequently differentiate in the presence of both CSF-1 and CSF-2. Page numbers are unavailable in our copy. (LLM, conf=0.88)

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Authors
Vogel, D. Y. S., Kooij, G., Heijnen, P. D. A. M., Breur, M., Peferoen, L. A. N., van der Valk, P., de Vries, H. E., Amor, S., & Dijkstra, C. D.
Affiliations
  • Amsterdam Neuroscience (NL)
  • Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
  • Department of Pathology, VU University Medical Center Amsterdam Amsterdam The Netherlands
  • Department of Molecular Cell Biology and Immunology VU University Medical Center Amsterdam, Neuroscience Campus Amsterdam The Netherlands
  • Queen Mary University of London (GB)
Corresponding author
Dijkstra, Christine D.
Venue
European Journal of Immunology
Publisher
Wiley
Published
2015-05-03
Volume
45
Issue
6
Pages
1808-1819
ISSN
  • 0014-2980 (ISSN-L)
  • 1521-4141
OpenAlex
W2131992889
Cited by
94
References
54
Citations by year
2026: 4 · 2025: 9 · 2024: 8 · 2023: 6 · 2022: 8 · 2021: 14 · 2020: 9 · 2019: 11 · 2018: 8 · 2017: 10 · 2016: 5 · 2015: 2
FWCI
6.62
Type
journal article
Language
en
Open access
Locations
  • European Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion, other-oa)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Funders
Dutch MS Research Foundation (09-358d)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords
GM-CSF, monocyte migration, blood-brain barrier, multiple sclerosis, microglia, macrophages, GM-CSF receptor, myeloid cell infiltration, neuroinflammation, astrocytes, macrophage activation
MeSH terms
Adult, Aged, Aged, 80 and over, Blood-Brain Barrier, Brain, Cells, Cultured, Female, Humans, Macrophage Activation, Macrophages, Male, Middle Aged, Monocytes, Multiple Sclerosis, Gene Expression, Granulocyte-Macrophage Colony-Stimulating Factor, Receptors, Granulocyte-Macrophage Colony-Stimulating Factor, Cytokines, Reactive Oxygen Species, Microglia, Endothelial Cells, Transendothelial and Transepithelial Migration

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