Astrocyte-Derived ATP Induces Vesicle Shedding and IL-1β Release from Microglia
Abstract
ATP has been indicated as a primary factor in microglial response to brain injury and inflammation. By acting on different purinergic receptors 2, ATP is known to induce chemotaxis and stimulate the release of several cytokines from these cells. The activation of purinergic receptors 2 in microglia can be triggered either by ATP deriving from dying cells, at sites of brain injury or by ATP released from astrocytes, in the absence of cell damage. By the use of a biochemical approach integrated with video microscopy experiments, we investigated the functional consequences triggered in microglia by ATP released from mechanically stimulated astrocytes, in mixed glial cocultures. Astrocyte-derived ATP induced in nearby microglia the formation and the shedding of membrane vesicles. Vesicle formation was inhibited by the ATP-degrading enzyme apyrase or by P2X7R antagonists. Isolation of shed vesicles, followed by IL-1β evaluation by a specific ELISA revealed the presence of the cytokine inside the vesicular organelles and its subsequent efflux into the extracellular medium. IL-1β efflux from shed vesicles was enhanced by ATP stimulation and inhibited by pretreatment with the P2X7 antagonist oxidized ATP, thus indicating a crucial involvement of the pore-forming P2X7R in the release of the cytokine. Our data identify astrocyte-derived ATP as the endogenous factor responsible for microvesicle shedding in microglia and reveal the mechanisms by which astrocyte-derived ATP triggers IL-1β release from these cells.
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- Authors
- Bianco, F., Pravettoni, E., Colombo, A., Schenk, U., Möller, T., Matteoli, M., & Verderio, C.
- Affiliations
- University of Milan (IT)
- Department Of Neurology, University of Washington , Seattle, WA 98195
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-06-01
- Volume
- 174
- Issue
- 11
- Pages
- 7268-7277
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1651376769
- Cited by
- 596
- References
- 46
- Citations by year
- 2026: 13 · 2025: 24 · 2024: 48 · 2023: 34 · 2022: 40 · 2021: 40 · 2020: 42 · 2019: 38 · 2018: 36 · 2017: 28 · 2016: 29 · 2015: 24 · 2014: 26 · 2013: 28 · 2012: 31
- FWCI
- 8.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Consiglio Nazionale delle Ricerche
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Keywords
- microglia, IL-1β release, P2X7 receptor, purinergic signaling, oxidized ATP, apyrase, neuroinflammation, brain injury
- MeSH terms
- Adenosine Triphosphate, Animals, Astrocytes, Cell Line, Cell Membrane, Hippocampus, Interleukin-1, Membrane Proteins, Microscopy, Fluorescence, Protein Processing, Post-Translational, Microglia, Receptors, Purinergic P2, Microscopy, Video, Coculture Techniques, Secretory Vesicles, Mice, Rats, Receptors, Purinergic P2X7
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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