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Cited by 223Neuroinflammation and Neurodegeneration MechanismsAdenosine and Purinergic SignalingExtracellular vesicles in disease

Microglial migration mediated by ATP-induced ATP release from lysosomes

Open access
Dou, Ying, Wu, Hang-jun, Li, Hui-quan, Qin, Song, Wang, Yin-er, Li, Jing, Lou, Hui-fang, Chen, Zhong +3 more·2012·Cell Research
DOI 10.1038/cr.2012.10PMC PMC3367529
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Abstract

Microglia are highly motile cells that act as the main form of active immune defense in the central nervous system. Attracted by factors released from damaged cells, microglia are recruited towards the damaged or infected site, where they are involved in degenerative and regenerative responses and phagocytotic clearance of cell debris. ATP release from damaged neural tissues has been suggested to mediate the rapid extension of microglial process towards the site of injury. However, the mechanisms of the long-range migration of microglia remain to be clarified. Here, we found that lysosomes in microglia contain abundant ATP and exhibit Ca(2+)-dependent exocytosis in response to various stimuli. By establishing an efficient in vitro chemotaxis assay, we demonstrated that endogenously-released ATP from microglia triggered by local microinjection of ATPγS is critical for the long-range chemotaxis of microglia, a response that was significantly inhibited in microglia treated with an agent inducing lysosome osmodialysis or in cells derived from mice deficient in Rab 27a (ashen mice), a small GTPase required for the trafficking and exocytosis of secretory lysosomes. These results suggest that microglia respond to extracellular ATP by releasing ATP themselves through lysosomal exocytosis, thereby providing a positive feedback mechanism to generate a long-range extracellular signal for attracting distant microglia to migrate towards and accumulate at the site of injury.

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  • PLCγ2 is similarly required in other peripheral immune cells to enable calcium mobilization upon B cell receptor activation using anti-IgM, FcεR ligation by IgE in mast cells, and FcγR activation in macrophages.

    “This observation adds to previous reports showing that PLCγ2 is similarly required in other peripheral immune cells to enable calcium mobilization upon B cell receptor activation using anti-IgM38, as well as FcεR ligation by IgE in mast cells and FcγR activation in macrophages10.”

    From PLCγ2 regulates TREM2 signalling and integrin-mediated adhesion and migration of human iPSC-derived macrophages (2021) · cites this paper as [38]

    The section on Ca²⁺-dependent lysosomal exocytosis reports ATP-induced calcium elevations in microglia, not PLCγ2-dependent responses to immune-receptor activation. Searches for PLCγ2, anti-IgM, FcεR and FcγR found no passage addressing the attributed claim about B cells, mast cells or macrophages. (LLM, conf=0.76)

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Authors
Dou, Y., Wu, H.-J., Li, H.-Q., Qin, S., Wang, Y.-E., Li, J., Lou, H.-F., Chen, Z., Li, X.-M., Luo, Q.-M., & Duan, S.
Affiliations
  • Chinese Academy of Sciences (CN)
  • Zhejiang University (CN)
Corresponding author
Duan, Shumin
ORCID
Venue
Cell Research
Publisher
Springer Science and Business Media LLC
Published
2012-01-10
Volume
22
Issue
6
Pages
1022-1033
ISSN
  • 1001-0602 (ISSN-L)
  • 1748-7838
DOI
10.1038/cr.2012.10
PMC
PMC3367529
OpenAlex
W2042640352
Cited by
223
References
3
Citations by year
2026: 5 · 2025: 16 · 2024: 19 · 2023: 12 · 2022: 22 · 2021: 19 · 2020: 17 · 2019: 14 · 2018: 17 · 2017: 14 · 2016: 13 · 2015: 17 · 2014: 16 · 2013: 15 · 2012: 7
FWCI
8.86
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Research (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (2011CB504400, 30730037)
  • Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
  • Zhejiang University
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
Keywords
microglial migration, extracellular ATP, lysosomal exocytosis, microglial chemotaxis, Rab27a, calcium-dependent exocytosis, neuroinflammation, central nervous system injury
MeSH terms
Adenosine Triphosphate, Animals, Calcium, Cell Movement, Cells, Cultured, Chemotaxis, Exocytosis, Lysosomes, Signal Transduction, Rats, Sprague-Dawley, Microglia, rab GTP-Binding Proteins, Mice, Rats, Receptors, Purinergic P2Y

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