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Modulation of Microglia by P2X and P2Y Receptors
Author(s) -
Campagno Keith,
Lu Wennan,
Albalawi Farraj,
Cenaj Aurora,
Tso HuenYee,
Mitchell Claire
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.501.1
Subject(s) - microglia , microbiology and biotechnology , purinergic receptor , receptor , p2y receptor , agonist , neuroglia , extracellular , stimulation , cytokine , signal transduction , neuroinflammation , biology , chemotaxis , chemokine , neuroscience , chemistry , central nervous system , inflammation , biochemistry , immunology
Microglial cells are involved in a complex series of physiologic and pathophysiologic interactions in the nervous system, and the receptors responsible for mediating these responses are central to coordinating these responses. ATP is a key extracellular signaling molecule in brain and retinal injury, and our previous results indicate release of ATP through pannexin hemichannels following mechanical injury to astrocytes. We ask here whether ATP alters migration, reactivation state and cytokine release in retinal and brain microglial cells. Using a Boyden chamber, ATP was shown to be a powerful chemoattractant for primary microglial cells isolated from both the brain and the retina. Detection of Hoechst‐labeled microglia on the lower side of the chamber peaked after 3 hours. Microglial migration was reduced by exposure of the cells to the P2Y12 antagonist ARC‐69931, while the P2X7 antagonist A839977 had no effect. Exposure of primed microglia to ATP led to the release of IL‐1β. This release was mimicked with P2X7‐specific agonist BzATP, and inhibited with antagonist A839977. Preliminary findings suggest ATP increased markers for the M1‐like activation state and decreasing the M2‐like activation state of microglial cells. Together these data suggest that stimulation of P2 receptors for ATP has a key role to play in migration, cytokine release and reactivate state of microglial cells. We speculate that ATP is a key signaling connection between astrocytes and microglia and helps link mechanical strain to inflammatory signaling in neural tissue. Support or Funding Information This work is supported by NIH Grants EY015537 and EY013434, and the Vision Research Core Grant EY001583. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .