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Updated: Jun 15, 2026

Two-photon Imaging of Microglial Processes' Attraction Toward ATP or Serotonin in Acute Brain Slices
07:27

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Published on: January 31, 2019

ATP induced microglial cell migration through non-transcriptional activation of matrix metalloproteinase-9

Min Sik Choi1, Kyu Suk Cho, Sun Mi Shin

  • 1Department of Pharmacology, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Korea.

Archives of Pharmacal Research
|March 3, 2010
PubMed

Insights

Adenosine triphosphate (ATP) triggers microglial migration to brain injury sites by increasing matrix metalloproteinase-9 (MMP-9) secretion. Inhibiting MMP-9 blocks this ATP-induced migration, revealing a key mechanism in neuroinflammation.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Microglia are key immune cells in the central nervous system (CNS) that respond to brain injury.
  • Adenosine triphosphate (ATP) released from damaged cells can attract microglia, but the underlying mechanisms are not fully understood.

Purpose of the Study:

  • To investigate how ATP influences microglial migration.
  • To determine if ATP regulates the activity of matrix metalloproteinases (MMPs), specifically MMP-9, in microglial migration.

Main Methods:

  • Assessed microglial migration in response to ATP.
  • Measured MMP-9 activity in culture supernatants using specific inhibitors (GM6001, SB-3CT).
  • Investigated the role of P2Y receptors and PI3K signaling pathways using antagonists and inhibitors (clopidogrel, wortmanin).

Main Results:

  • ATP significantly increased microglial migration and MMP-9 activity in a concentration-dependent manner.
  • Increased MMP-9 activity resulted from enhanced protein secretion, not altered gene or protein expression.
  • Inhibiting MMP-9, P2Y receptors, or PI3K pathways blocked ATP-induced microglial migration.

Conclusions:

  • ATP non-transcriptionally enhances MMP-9 activity via P2Y and PI3K signaling, promoting microglial migration.
  • This mechanism provides insight into regulating MMP-9 activity during microglial migration.
  • Findings are relevant to inflammatory responses in neurodegenerative disorders.

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