Antigen induced hyperreactivity to histamine is vagally mediated

Richard W. Costello, Christopher M. Evans, Bethany L. Yost, Gerard J. Gleich, David B. Jacoby, Allison D. Fryer

Research output: Contribution to journalArticle

Abstract

Pulmonary M2 muscarinic receptors limit acetylcholine release from parasympathetic nerves. In antigen challenged guinea pigs these M2 muscarinic receptors are dysfunctional which leads to increased vagally mediated bronchoconstriction. Dysfunction of these receptors may be due to eosinophil major basic protein which is an antagonist at these receptors. Histamine causes bronchoconstriction by a direct effect on smooth muscle and by activating a vagal reflex. Since 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 anaesthetized antigen challenged guinea pigs histamine induced bronchoconstriction (1-20 nmol/kg i.v.) was greater than in controls. After vagotomy or atropine (1mgkg i.v.) treatment the response to histamine in antigen challenged animals was the same as in controls. In antigen challenged animals antibody pretreatment to block eosinophil influx into the airways, with an antibody to the adhesion molecule VLA-4 or using an antibody to eosinophil major basic protein prevented the development of antigen induced hyperreactivity to histamine. Thus, hyperreactivity to histamine is vagally mediated and dependent on the recruitment and degranulation of eosinophils.

Original languageEnglish (US)
Pages (from-to)A50
JournalThorax
Volume52
Issue numberSUPPL. 6
StatePublished - Dec 1 1997
Externally publishedYes

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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  • Cite this

    Costello, R. W., Evans, C. M., Yost, B. L., Gleich, G. J., Jacoby, D. B., & Fryer, A. D. (1997). Antigen induced hyperreactivity to histamine is vagally mediated. Thorax, 52(SUPPL. 6), A50.