Yost B L, Gleich G J, Fryer A D
Department of Environmental Health Sciences, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA.
J Appl Physiol (1985). 1999 Oct;87(4):1272-8. doi: 10.1152/jappl.1999.87.4.1272.
Control of airway smooth muscle is provided by parasympathetic nerves that release acetylcholine onto M(3) muscarinic receptors. Acetylcholine release is limited by inhibitory M(2) muscarinic receptors. In antigen-challenged guinea pigs, hyperresponsiveness is due to blockade of neuronal M(2) receptors by eosinophil major basic protein (MBP). Because exposure of guinea pigs to ozone also causes M(2) dysfunction and airway hyperresponsiveness, the role of eosinophils in ozone-induced hyperresponsiveness was tested. Animals were exposed to filtered air or to 2 parts/million ozone for 4 h. Twenty-four hours later, the muscarinic agonist pilocarpine no longer inhibited vagally induced bronchoconstriction in ozone-exposed animals, indicating M(2) dysfunction. M(2) receptor function in ozone-exposed animals was protected by depletion of eosinophils with antibody to interleukin-5 and by pretreatment with antibody to guinea pig MBP. M(2) function was acutely restored by removal of MBP with heparin. Ozone-induced hyperreactivity was also prevented by antibody to MBP and was reversed by heparin. These data show that loss of neuronal M(2) receptor function after ozone is due to release of eosinophil MBP.
气道平滑肌的控制由副交感神经提供，这些神经将乙酰胆碱释放到M(3)毒蕈碱受体上。乙酰胆碱的释放受到抑制性M(2)毒蕈碱受体的限制。在抗原激发的豚鼠中，高反应性是由于嗜酸性粒细胞主要碱性蛋白(MBP)对神经元M(2)受体的阻断。由于豚鼠暴露于臭氧也会导致M(2)功能障碍和气道高反应性，因此对嗜酸性粒细胞在臭氧诱导的高反应性中的作用进行了测试。将动物暴露于过滤空气或2 ppm臭氧中4小时。24小时后，毒蕈碱激动剂毛果芸香碱不再抑制臭氧暴露动物中迷走神经诱导的支气管收缩，表明M(2)功能障碍。用抗白细胞介素-5抗体使嗜酸性粒细胞耗竭以及用抗豚鼠MBP抗体预处理可保护臭氧暴露动物的M(2)受体功能。用肝素去除MBP可使M(2)功能急性恢复。抗MBP抗体也可预防臭氧诱导的高反应性，肝素可使其逆转。这些数据表明，臭氧后神经元M(2)受体功能的丧失是由于嗜酸性粒细胞MBP的释放。
