Antigen-induced hyperreactivity to histamine: role of the vagus nerves and eosinophils.
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.
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000941:Antigens / Q000276:immunology*; D001285:Atropine / Q000494:pharmacology; D001798:Blood Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D016084:Bronchoconstriction / Q000187:drug effects* / Q000276:immunology*; D003959:Diamines / Q000494:pharmacology; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000502:physiology*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D039041:Integrin alpha4beta1; D016023:Integrins / Q000037:antagonists & inhibitors / Q000502:physiology; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D043585:Receptor, Muscarinic M2; D016201:Receptors, Lymphocyte Homing / Q000037:antagonists & inhibitors / Q000502:physiology; D011976:Receptors, Muscarinic / Q000502:physiology; D012260:Ribonucleases; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology*