Pretreatment with antibody to eosinophil major basic protein prevents hyperresponsiveness by protecting neuronal M2 muscarinic receptors in antigen-challenged guinea pigs

Christopher M. Evans, Allison Fryer, David Jacoby, Gerald J. Gleich, Richard W. Costello

Research output: Contribution to journalArticle

158 Citations (Scopus)

Abstract

In antigen-challenged guinea pigs there is recruitment of eosinophils into the lungs and to airway nerves, decreased function of inhibitory M2 muscarinic autoreceptors on parasympathetic nerves in the lungs, and airway hyperresponsiveness. A rabbit antibody to guinea pig eosinophil major basic protein was used to determine whether M2 muscarinic receptor dysfunction, and the subsequent hyperresponsiveness, are due to antagonism of the M2 receptor by eosinophil major basic protein. Guinea pigs were sensitized, challenged with ovalbumin and hyperresponsiveness, and M2 receptor function tested 24 h later with the muscarinic agonist pilocarpine. Antigen-challenged guinea pigs were hyperresponsive to electrical stimulation of the vagus nerves compared with controls. Likewise, loss of M2 receptor function was demonstrated since the agonist pilocarpine inhibited vagally-induced bronchoconstriction in control but not challenged animals. Pretreatment with rabbit antibody to guinea pig eosinophil major basic protein prevented hyperresponsiveness, and protected M2 receptor function in the antigen- challenged animals without inhibiting eosinophil accumulation in the lungs or around the nerves. Thus, hyperresponsiveness is a result of inhibition of neuronal M2 muscarinic receptor function by eosinophil major basic protein in antigen-challenged guinea pigs.

Original languageEnglish (US)
Pages (from-to)2254-2262
Number of pages9
JournalJournal of Clinical Investigation
Volume100
Issue number9
StatePublished - Nov 1 1997
Externally publishedYes

Fingerprint

Eosinophil Major Basic Protein
Muscarinic M2 Receptors
Guinea Pigs
Antigens
Antibodies
Pilocarpine
Eosinophils
Lung
Rabbits
Muscarinic Agonists
Autoreceptors
Vagus Nerve
Bronchoconstriction
Ovalbumin
Cholinergic Agents
Electric Stimulation

Keywords

  • Airway hyperresponsiveness
  • Antigen challenge
  • Eosinophils
  • Major basic protein
  • Muscarinic receptors
  • Parasympathetic nerves

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Pretreatment with antibody to eosinophil major basic protein prevents hyperresponsiveness by protecting neuronal M2 muscarinic receptors in antigen-challenged guinea pigs. / Evans, Christopher M.; Fryer, Allison; Jacoby, David; Gleich, Gerald J.; Costello, Richard W.

In: Journal of Clinical Investigation, Vol. 100, No. 9, 01.11.1997, p. 2254-2262.

Research output: Contribution to journalArticle

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