ATP and NO dually control migration of microglia to nerve lesions

Yuanli Duan, Christie L. Sahley, Kenneth J. Muller

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Microglia migrate rapidly to lesions in the central nervous system (CNS), presumably in response to chemoattractants including ATP released directly or indirectly by the injury. Previous work on the leech has shown that nitric oxide (NO), generated at the lesion, is both a stop signal for microglia at the lesion and crucial for their directed migration from hundreds of micrometers away within the nerve cord, perhaps mediated by a soluble guanylate cyclase (sGC). In this study, application of 100 μM ATP caused maximal movement of microglia in leech nerve cords. The nucleotides ADP, UTP, and the nonhydrolyzable ATP analog AMP-PNP (adenyl-5′-yl imidodiphosphate) also caused movement, whereas AMP, cAMP, and adenosine were without effect. Both movement in ATP and migration after injury were slowed by 50 μM reactive blue 2 (RB2), an antagonist of purinergic receptors, without influencing the direction of movement. This contrasted with the effect of the NO scavenger cPTIO (2-(4-carboxyphenyl)-4,4,5,5-terame-thylimidazoline-oxyl-3-oxide), which misdirected movement when applied at 1 mM. The cPTIO reduced cGMP immunoreactivity without changing the immunoreactivity of eNOS (endothelial nitric oxide synthase), which accompanies increased NOS activity after nerve cord injury, consistent with involvement of sGC, Moreover, the sGC-specific inhibitor LY83583 applied at 50 μM had a similar effect, in agreement with previous results with methylene blue. Taken together, the experiments support the hypothesis that ATP released directly or indirectly by injury activates microglia to move, whereas NO that activates sGC directs migration of microglia to CNS lesions.

Original languageEnglish (US)
Pages (from-to)60-72
Number of pages13
JournalDevelopmental Neurobiology
Volume69
Issue number1
DOIs
StatePublished - Jan 2009

Keywords

  • Cell movement
  • CNS injury
  • Leeches
  • Nerve injury
  • Nerve regeneration
  • Purinergic receptors

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience

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