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Published on: January 7, 2020

Activation of the adenosine-A3 receptor stimulates matrix metalloproteinase-9 secretion by macrophages

Emilie Velot1, Benjamin Haas, Frédérique Léonard

  • 1Laboratory of Cardiovascular Research, CRP-Santé, Luxembourg, Luxembourg.

Cardiovascular Research
|July 26, 2008
PubMed
Abstract

Insights

Adenosine (Ado) boosts matrix metalloproteinase-9 (MMP-9) secretion in macrophages via the A3 receptor, contrasting its effect on neutrophils. This finding is crucial for understanding myocardial infarction (MI) and developing targeted therapies.

Area of Science:

  • Cardiovascular Biology
  • Immunology
  • Molecular Medicine

Background:

  • Matrix metalloproteinase-9 (MMP-9) is implicated in ventricular remodeling post-myocardial infarction (MI).
  • Adenosine (Ado), a cardioprotectant, may influence ventricular remodeling.
  • Previous studies show Ado inhibits MMP-9 secretion in human neutrophils.

Purpose of the Study:

  • To investigate the effect of adenosine on MMP-9 production in human macrophages.
  • To elucidate the receptor mechanism underlying adenosine's action on MMP-9 in macrophages.

Main Methods:

  • Human monocytes and a monocyte cell line were differentiated into macrophages.
  • Macrophages were treated with adenosine and activated by hypoxia or Toll-like receptor-4 ligands.
  • Adenosine receptor subtypes were manipulated using agonists, antagonists, and silencing techniques.

Main Results:

  • Adenosine dose- and time-dependently enhanced MMP-9 secretion by macrophages.
  • Increased endogenous adenosine also elevated MMP-9 secretion.
  • Adenosine-mediated enhancement of MMP-9 was linked to the A3 receptor.
  • Adenosine improved monocyte migration, an effect dependent on MMP-9 activity.
  • MMP-9 expression was elevated in blood cells from acute MI patients.

Conclusions:

  • Adenosine stimulates MMP-9 secretion in macrophages via the A3 receptor.
  • This contrasts with adenosine's inhibitory effect on MMP-9 in neutrophils (via A2a receptor).
  • Findings suggest potential therapeutic strategies targeting adenosine receptors in MI.

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