Eosinophils and airway nerves in asthma.
In the lungs, neuronal M2 muscarinic receptors limit the release of acetylcholine from postganglionic cholinergic nerves. However, these receptors are not functional under certain circumstances in animal models of hyperreactivity such as occurs after exposure of sensitised animals to an allergen or during a respiratory tract virus infection. This loss of M2 receptor function leads to an increase in acetylcholine release from cholinergic nerves and thus is a mechanism for the vagally mediated hyperreactivity seen in these animals. Studies in animal models of hyperreactivity have shown that eosinophils localise to the airway nerves of sensitised animals after antigen challenge. Inhibiting this localisation of eosinophils either with an antibody to the eosinophil survival cytokine IL-5 or the eosinophil adhesion molecule VLA-4 prevents loss of M2 muscarinic receptor function. It is likely that eosinophil MBP is responsible for the loss of M2 receptor function, since inhibiting eosinophil MBP with an antibody or neutralising MBP with heparin prevents this loss of function. These data are also supported by ligand binding studies where it has been shown that eosinophil MBP is an allosteric antagonist at neuronal M2 muscarinic receptors. Loss of function of lung neuronal M2 muscarinic receptors may also occur under certain circumstances in patients with asthma, although the mechanisms are not yet established.
Costello
R W
RW
Department of Medicine, University of Liverpool, United Kingdom.
Jacoby
D B
DB
Gleich
G J
GJ
Fryer
A D
AD
D000818:Animals; D001249:Asthma / Q000276:immunology / Q000473:pathology*; D001798:Blood Proteins / Q000276:immunology / Q000378:metabolism; D016084:Bronchoconstriction / Q000502:physiology; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000276:immunology*; D006168:Guinea Pigs; D006801:Humans; D008168:Lung / Q000294:innervation*; D009474:Neurons / Q000502:physiology; D010275:Parasympathetic Nervous System / Q000276:immunology*; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D012260:Ribonucleases; D014630:Vagus Nerve / Q000276:immunology
D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic; D012260:Ribonucleases