Rod-Shaped monocytes patrol the brain vasculature and give rise to perivascular macrophages under the influence of proinflammatory cytokines and angiopoietin-2
Open accessAbstract
The nervous system is constantly infiltrated by blood-derived sentinels known as perivascular macrophages. Their immediate precursors have not yet been identified in situ and the mechanism that governs their recruitment is mostly unknown. Here, we provide evidence that CD68+GR1−monocytes can give rise to perivascular macrophages in mice suffering from endotoxemia. After adhesion to the endothelium, these monocytes start to crawl, adopt a rod-shaped morphology when passing through capillaries, and can manifest the ability to proliferate and form a long cytoplasmic protuberance. They are attracted in greater numbers during endotoxemia by a combination of vasoregulatory molecules, including TNF (tumor necrosis factor), interleukin-1β, and angiopoietin-2. After a period of several hours, some of them cross the endothelium to expand the population of perivascular macrophages. Depletion of adherent monocytes and perivascular macrophages can be achieved by injection of anti-angiopoietin-2 peptide-Fc fusion protein. This study extends our understanding of the behavior of monocytes at the blood–brain interface and provides a way to block their infiltration into the nervous tissue under inflammatory conditions.
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Non-classical monocytes are known as patrolling monocytes, named for their role in surveilling the vasculature and crossing the blood brain barrier to remove damaged tissue, including amyloid plaques.
“Non-classical monocytes are known as patrolling monocytes, named for their role in surveilling the vasculature and crossing the blood brain barrier to remove damaged tissue, including amyloid plaques.39–41”
From TET2-mutant myeloid cells mitigate Alzheimer’s disease progression via CNS infiltration and enhanced phagocytosis in mice (2025) · cites this paper as [40]
The Discussion (page unavailable) reports that type 2 monocytes crawl on cerebral blood vessels and can give rise to perivascular macrophages; the Introduction discusses monocyte traffic across the blood–brain barrier. The paper does not say that these monocytes cross it to remove damaged tissue or amyloid plaques. (LLM, conf=0.88)
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- Authors
- Audoy-Rémus, J., Richard, J.-F., Soulet, D., Zhou, H., Kubes, P., & Vallières, L.
- Affiliations
- Université Laval (CA)
- Centre hospitalier de l'Université Laval (CA)
- Lund University (SE)
- University of Calgary (CA)
- Corresponding author
- Vallières, Luc
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-10-08
- Volume
- 28
- Issue
- 41
- Pages
- 10187-10199
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6671016
- OpenAlex
- W1985291892
- Cited by
- 93
- References
- 8
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 4 · 2021: 10 · 2020: 2 · 2019: 2 · 2018: 3 · 2017: 8 · 2016: 8 · 2015: 7 · 2014: 9 · 2013: 8 · 2012: 5
- FWCI
- 3.74
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Amgen
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council of Canada
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- perivascular macrophages, monocyte-to-macrophage differentiation, blood-brain barrier, endotoxemia, angiopoietin-2, TNF-α, IL-1β, inflammatory cytokines, neuroinflammation, monocyte depletion
- MeSH terms
- CD68 Molecule, Animals, Blood Vessels, Brain, Cell Count, Cell Movement, Macrophages, Mice, Inbred C57BL, Mice, Transgenic, Monocytes, Phenotype, Tumor Necrosis Factor-alpha, Antigens, Differentiation, Myelomonocytic, Antigens, CD, Cytokines, Inflammation Mediators, Endotoxemia, Angiopoietin-2, Cell Shape, Cell Proliferation, Green Fluorescent Proteins, Mice, Interleukin-1beta
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