Microglial phagocytosis attenuated by short-term exposure to exogenous ATP through P2X7 receptor action

Kuan Min Fang, Chung Shi Yang, Synthia H. Sun, Shun Fen Tzeng

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)

Abstract

Microglia, the CNS resident macrophages responsible for the clearance of degenerating cellular fragments, are essential to tissue remodeling and repair after CNS injury. ATP can be released in large amounts after CNS injury and may mediate microglial activity through the ionotropic P2X and the metabotropic P2Y receptors. This study indicates that exposure to a high concentration of ATP for 30 min rapidly induces changes of the microglial cytoskeleton, and significantly attenuates microglial phagocytosis. A pharmacological approach showed that ATP-induced inhibition of microglial phagocytotic activity was due to P2X7R activation, rather than that of P2YR. Activation of P2X 7R by its agonist, 2′-3′-O-(4-benzoyl)benzoyl-ATP (BzATP), produced a Ca2+-independent reduction in microglial phagocytotic activity. In addition, the knockdown of P2X7R expression by lentiviral-mediated shRNA interference or the blockade of P2X7R activation by the specific antagonists, oxidized ATP (oxATP) and brilliant blue G, has efficiently restored the phagocytotic activity of ATP and BzATP-treated microglia. Our results reveal that P2X7R activation may induce the formation of a Ca2+-independent signaling complex, which results in the reduction of microglial phagocytosis. This suggests that exposure to ATP for a short-term period may cause insufficient clearance of tissue debris by microglia through P2X7R activation after CNS injury, and that blockade of this receptor may preserve the phagocytosis of microglia and facilitate CNS tissue repair.

Original languageEnglish
Pages (from-to)1225-1237
Number of pages13
JournalJournal of Neurochemistry
Volume111
Issue number5
DOIs
Publication statusPublished - 2009 Dec

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

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