Antigen-induced hyperreactivity to histamine: Role of the vagus nerves and eosinophils

Richard W. Costello, Christopher M. Evans, Bethany L. Yost, Kristen E. Belmonte, Gerald J. Gleich, David B. Jacoby, Allison D. Fryer

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

M2 muscarinic receptors limit acetylcholine release from the pulmonary parasympathetic nerves. M2 receptors are dysfunctional in antigen-challenged guinea pigs, causing increased vagally mediated bronchoconstriction. Dysfunction of these M2 receptors is due to eosinophil major basic protein, which is an antagonist for M2 receptors. Histamine-induced bronchoconstriction is composed of a vagal reflex in addition to its direct effect on airway smooth muscle. Because hyperreactivity to histamine is seen in antigen-challenged animals, we hypothesized that hyperreactivity to histamine may be due to increased vagally mediated bronchoconstriction caused by dysfunction of M2 receptors. In anesthetized, antigen-challenged guinea pigs, histamine-induced bronchoconstriction was greater than that in control guinea pigs. After vagotomy or atropine treatment, the response to histamine in antigen-challenged animals was the same as that in control animals. In antigen-challenged animals, blockade of eosinophil influx into the airways or neutralization of eosinophil major basic protein prevented the development of hyperreactivity to histamine. Thus hyperreactivity to histamine in antigen- challenged guinea pigs is vagally mediated and dependent on eosinophil major basic protein.

Original languageEnglish (US)
Pages (from-to)L709-L714
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume276
Issue number5 20-5
DOIs
StatePublished - May 1999
Externally publishedYes

Keywords

  • Adhesion molecules
  • Inflammation
  • Major basic protein
  • Muscarinic receptors
  • Parasympathetic nerves

ASJC Scopus subject areas

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

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