Cited by 134Complement system in diseasesGlycosylation and Glycoproteins ResearchNeuroinflammation and Neurodegeneration Mechanisms

Sialic acid on the neuronal glycocalyx prevents complement C1 binding and complement receptor-3-mediated removal by microglia

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Linnartz, Bettina, Kopatz, Jens, Tenner, Andrea J., Neumann, Harald·2012·The Journal of Neuroscience

Abstract

Microglial cells are professional phagocytes of the CNS responsible for clearance of unwanted structures. Neuronal processes are marked by complement C1 before they are removed in development or during disease processes. Target molecules involved in C1 binding and mechanisms of clearance are still unclear. Here we show that the terminal sugar residue sialic acid of the mouse neuronal glycocalyx determines complement C1 binding and microglial-mediated clearance function. Several early components of the classical complement cascade including C1q, C1r, C1s, and C3 were produced by cultured mouse microglia. The opsonin C1q was binding to neurites after enzymatic removal of sialic acid residues from the neuronal glycocalyx. Desialylated neurites, but not neurites with intact sialic acid caps, were cleared and taken up by cocultured microglial cells. The removal of the desialylated neurites was mediated via the complement receptor-3 (CR3; CD11b/CD18). Data demonstrate that mouse microglial cells via CR3 recognize and remove neuronal structures with an altered neuronal glycocalyx lacking terminal sialic acid.

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Crossref · 10.1523/jneurosci.3830-11.2012

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  • The complement participates in the physiological process termed synaptic pruning; synapses and axons have to be labeled by complement components C1q and C3 before being phagocytosed, which prompts their selective recognition by microglial cells.

    “The complement also participates in the physiological process, termed synaptic pruning. The synapses and axons have to be labeled by complement components C1q and C3 before being phagocytosed, which prompts their selective recognition by microglial cells (Paolicelli et al., 2011; Linnartz et al., 2012; Schafer et al., 2012).”

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Authors
Linnartz, B., Kopatz, J., Tenner, A. J., & Neumann, H.
Affiliations
  • University of Bonn (DE)
  • University of California, Irvine (US)
  • University Hospital Bonn (DE)
Corresponding author
Neumann, Harald
Venue
The Journal of Neuroscience
Published
2012-01-18
Volume
32
Issue
3
Pages
946-952
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W2167842125
Cited by
134
References
28
Citations by year
2026: 5 · 2025: 6 · 2024: 10 · 2023: 7 · 2022: 10 · 2021: 18 · 2020: 12 · 2019: 6 · 2018: 6 · 2017: 10 · 2016: 4 · 2015: 11 · 2014: 13 · 2013: 8 · 2012: 7
FWCI
5.43
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Deutsche Forschungsgemeinschaft (KFO177, SFB 704, FOR1336)
  • National Institutes of Health (SFB704, AG00538)
  • University of California, Irvine
  • National Institute on Aging (P01AG000538, AG 00538)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
sialic acid, complement C1, C1q, complement receptor 3, CD11b/CD18, microglial phagocytosis, desialylation, classical complement pathway, C1r, C1s, complement C3
MeSH terms
Analysis of Variance, Animals, Animals, Newborn, Brain, Cells, Cultured, Complement C3, Embryo, Mammalian, Female, Flow Cytometry, Gene Expression Regulation, Humans, Lipopolysaccharides, Male, Mice, Inbred C57BL, Neuraminidase, Neurons, Protein Binding, Receptors, Complement, Sialic Acids, Transfection, Tubulin, Antigens, CD, Complement C1q, Cytokines, Microglia, Coculture Techniques, Glycocalyx, CD11b Antigen, Green Fluorescent Proteins, Mice

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