Role of macrophages in virus-induced airway hyperresponsiveness and neuronal M2 muscarinic receptor dysfunction

Ann M. Lee, Allison D. Fryer, Nico Van Rooijen, David B. Jacoby

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


Viral infections exacerbate asthma. One of the pathways by which viruses trigger bronchoconstriction and hyperresponsiveness is by causing dysfunction of inhibitory M2 muscarinic receptors on the airway parasympathetic nerves. These receptors normally limit acetylcholine (ACh) release from the parasympathetic nerves. Loss of M2 receptor function increases ACh release, thereby increasing vagally mediated bronchoconstriction. Because viral infection causes an influx of macrophages into the lungs, we tested the role of macrophages in virus-induced airway hyperresponsiveness and M2 receptor dysfunction. Guinea pigs infected with parainfluenza virus were hyperresponsive to electrical stimulation of the vagus nerves but not to intravenous ACh, indicating that hyperresponsiveness was due to increased release of ACh from the nerves. In addition, the muscarinic agonist pilocarpine no longer inhibited vagally induced bronchoconstriction, indicating M 2 receptor dysfunction. Treating animals with liposome-encapsulated dichloromethylene-diphosphonate depleted macrophages as assessed histologically. In these animals, viral infection did not cause airway hyperresponsiveness or M2 receptor dysfunction. These data suggest that macrophages mediate virus-induced M2 receptor dysfunction and airway hyperresponsiveness.

Original languageEnglish (US)
Pages (from-to)L1255-L1259
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number6 30-6
StatePublished - Jun 2004


  • Asthma
  • Clodronate
  • Liposomes
  • Parasympathetic
  • Vagal

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology


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