Ozone induced hyperresponsiveness and blockade of m2 muscarinic receptors by eosinophil major basic protein. Yost, Bethany L, Gerald J Gleich and Allison D Fryer. Department of Environmental Health Sciences, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, MD, 21205 USA, *Departments of Immunology and Medicine, Mayo Clinic, Rochester, MN, 55905 USA.
APStracts 6:0245A, 1999.
Control of airway smooth muscle is provided by parasympathetic nerves which release acetylcholine onto M3 muscarinic receptors. Acetylcholine release is limited by inhibitory M2 muscarinic receptors. In antigen challenged guinea pigs hyperresponsiveness is due to blockade of neuronal M2 receptors by eosinophil major basic protein (MBP). Since exposure of guinea pigs to ozone also causes M2 dysfunction and airway hyperresponsiveness, the role of eosinophils in ozone induced hyperresponsiveness was tested. Animals were exposed to filtered air or 2 ppm ozone for 4 hours. Twenty four hours later, the muscarinic agonist, pilocarpine no longer inhibited vagally induced bronchoconstriction in ozone exposed animals indicating M2 dysfunction. M2 receptor function in ozone exposed animals was protected by depletion of eosinophils with AbIL-5, and by pretreatment with Ab guinea-pig MBP. M2 function was acutely restored by removal of MBP with heparin. Ozone induced hyperreactivity was also prevented by AbMBP and reversed by heparin. These data show that loss of neuronal M2 receptor function after ozone is due to release of eosinophil MBP. 

Received 23 December 1998; accepted in final form 26 May 1999.
APS Manuscript Number A1169-8.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1999 The American Physiological Society.
Published in APStracts on 14 June 1999