Effects of dexamethasone on antigen-induced airway eosinophilia and M2 receptor dysfunction

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35 Scopus citations

Abstract

In antigen-challenged guinea pigs, airway hyperreactivity is due to recruitment of eosinophils to the airway nerves and dysfunction of M2 muscarinic receptors. M2 receptor dysfunction is caused by eosinophil major basic protein, which is an allosteric antagonist at the receptor. Because glucocorticoids inhibit airway hyperreactivity in humans and in animal models of asthma, we tested whether dexamethasone treatment (6 μg · kg-1 · d-1 for 3 d, intraperitoneal) before antigen challenge prevents M2 receptor dysfunction and airway hyperreactivity. Guinea pigs were sensitized to ovalbumin via intraperitoneal injections, and were challenged with ovalbumin via inhalation. Twenty-four hours later, hyperreactivity and M2 receptor function were tested. Antigen-challenged animals were hyperreactive to vagal stimulation, and demonstrated loss of M2 receptor function. Dexamethasone pretreatment prevented hyperreactivity and M2 receptor dysfunction in antigen-challenged guinea pigs. Antigen challenge resulted in recruitment of eosinophils to the airways and to the airway nerves. Dexamethasone prevented recruitment of eosinophils to the airway nerves but did not affect total eosinophil influx into the airways. These results demonstrate that dexamethasone prevents antigen-induced hyperreactivity by protecting neuronal M2 muscarinic receptors from antagonism by eosinophil major basic protein, and this protective mechanism appears to be by specifically inhibiting eosinophil recruitment to the airway nerves.

Original languageEnglish (US)
Pages (from-to)1484-1492
Number of pages9
JournalAmerican journal of respiratory and critical care medicine
Volume163
Issue number6
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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