Eosinophil recruitment to the airway nerves

Jacoby, David B.; Costello, Richard M.; Fryer, Allison D.

doi:10.1067/mai.2001.112940

« Previous Next »The Journal of Allergy and Clinical Immunology
Volume 107, Issue 2 , Pages 211-218, February 2001

Eosinophil recruitment to the airway nerves☆☆☆

Baltimore, Md, and Dublin, Ireland

From ^athe Division of Pulmonary and Critical Care Medicine, Johns Hopkins Asthma and Allergy Center, Johns Hopkins University, Baltimore; ^bthe Department of Medicine, RCSI, Beaumont Hospital, University of Dublin; and ^cthe Department of Environmental Health Sciences, School of Hygiene and Public Health, Johns Hopkins University, Baltimore

Received 18 October 2000; received in revised form 13 November 2000; accepted 13 November 2000.

Abstract

Increased vagal reflexes contribute to bronchoconstriction in asthma. Antigen challenge of sensitized animals induces vagal hyperresponsiveness. This review will discuss the evidence that eosinophils increase release of acetylcholine from the parasympathetic nerves. After antigen challenge, eosinophils are actively recruited to the airway nerves, possibly through expression of chemotactic substances and adhesion molecules by the nerves. Tachykinins acting on neurokinin 1 receptors activate the eosinophils. Activated eosinophils release eosinophil major basic protein (MBP), which is an endogenous antagonist for M₂ muscarinic receptors. The M₂ muscarinic receptors on the parasympathetic nerves in the lungs normally inhibit release of acetylcholine. When M₂ receptors are blocked by MBP, acetylcholine release is increased, resulting in hyperresponsiveness. Neutralization of MBP with polyanionic substances restores M₂ receptor function and eliminates hyperresponsiveness. Antibodies to MBP prevent M₂ receptor dysfunction and hyperresponsiveness, as do antibodies to the adhesion molecule very late antigen 4, which prevent eosinophil migration. A low dose of dexamethasone, which does not affect total eosinophil influx into the lungs and airways, prevents eosinophils from clustering around the nerves and prevents antigen-induced M₂ dysfunction and hyperresponsiveness. Furthermore, animal studies show that viral infections, which are important precipitants of asthma attacks, and exposure to air pollutants such as ozone can also activate airway eosinophils, leading to a chain of events similar to that seen after antigen challenge. Finally, a similar clustering of eosinophils around airway nerves, as well as release of MBP onto the nerves, is seen in fatal asthma, suggesting that similar mechanisms may be involved in human airway hyperresponsiveness. (J Allergy Clin Immunol 2001;107:211-8.)

Keywords: Muscarinic receptors, asthma, parasympathetic nerves, hyperresponsiveness, bronchoconstriction

Abbreviations: ICAM: , Intracellular adhesion molecule, MBP: , Major basic protein, NK: , Neurokinin, VCAM: , Vascular cell adhesion molecule, VLA: , Very late antigen