Ozone-induced hyperresponsiveness and blockade of M2 muscarinic receptors by eosinophil major basic protein

Bethany L. Yost, Gerald J. Gleich, Allison Fryer

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Control of airway smooth muscle is provided by parasympathetic nerves that release acetylcholine onto M3 muscarinic receptors. Acetylcholine release is limited by inhibitory M2 muscarinic receptors. In antigen- challenged guinea pigs, hyperresponsiveness is due to blockade of neuronal M2 receptors by eosinophil major basic protein (MBP). Because exposure of guinea pigs to ozone also causes M2 dysfunction and airway hyperresponsiveness, the role of eosinophils in ozone-induced hyperresponsiveness was tested. Animals were exposed to filtered air or to 2 parts/million ozone for 4 h. Twenty-four hours later, the muscarinic agonist pilocarpine no longer inhibited vagally induced bronchoconstriction in ozone- exposed animals, indicating M2 dysfunction. M2 receptor function in ozone- exposed animals was protected by depletion of eosinophils with antibody to interleukin-5 and by pretreatment with antibody to guinea pig MBP. M2 function was acutely restored by removal of MBP with heparin. Ozone-induced hyperreactivity was also prevented by antibody to MBP and was reversed by heparin. These data show that loss of neuronal M2 receptor function after ozone is due to release of eosinophil MBP.

Original languageEnglish (US)
Pages (from-to)1272-1278
Number of pages7
JournalJournal of Applied Physiology
Volume87
Issue number4
StatePublished - Oct 1999
Externally publishedYes

Fingerprint

Eosinophil Major Basic Protein
Muscarinic M2 Receptors
Ozone
Guinea Pigs
Eosinophils
Acetylcholine
Heparin
Antibodies
Muscarinic M3 Receptors
Muscarinic Agonists
Proteins
Pilocarpine
Airway Management
Bronchoconstriction
Interleukin-5
Smooth Muscle
Air
Antigens

Keywords

  • Asthma
  • Hyperreactivity
  • Inflammation
  • Neuronal receptors

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

Ozone-induced hyperresponsiveness and blockade of M2 muscarinic receptors by eosinophil major basic protein. / Yost, Bethany L.; Gleich, Gerald J.; Fryer, Allison.

In: Journal of Applied Physiology, Vol. 87, No. 4, 10.1999, p. 1272-1278.

Research output: Contribution to journalArticle

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