Pretreatment with antibody to eosinophil major basic protein prevents hyperresponsiveness by protecting neuronal M-2 muscarinic receptors in antigen-challenged guinea pigs
Pretreatment with antibody to eosinophil major basic protein prevents hyperresponsiveness by protecting neuronal M-2 muscarinic receptors in antigen-challenged guinea pigs
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DOI：
10.1172/jci119763
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发表时间：
1997-11-01
影响因子：
15.9
通讯作者：
Costello, RW
中科院分区：
文献类型：
--
作者：
Evans, CM;Fryer, AD;Costello, RW
在抗原激发的豚鼠中，嗜酸性粒细胞聚集到肺部和气道神经中，抑制M-2毒蕈碱自身受体在肺部副交感神经上的功能下降，气道高反应性。兔抗豚鼠嗜酸性粒细胞主要碱性蛋白抗体用于确定M-2毒蕈碱受体功能障碍和随后的高反应性是否由于嗜酸性粒细胞主要碱性蛋白对M-2受体的拮抗所致。豚鼠致敏，卵清蛋白和高反应性刺激，24小时后用毒蕈碱激动剂匹罗卡平检测M-2受体功能。与对照组相比，抗原激发豚鼠对迷走神经的电刺激反应过度。同样，M-2受体功能的丧失也被证实，因为激动剂匹罗卡品抑制了迷走神经诱导的支气管收缩，而不是刺激动物。兔抗豚鼠嗜酸性粒细胞主要碱性蛋白抗体预处理可防止高反应性，保护Mt受体功能，但不抑制肺或神经周围嗜酸性粒细胞的积累。因此，高反应性是抗原刺激豚鼠中嗜酸性粒细胞主要碱性蛋白抑制神经元M-2毒蕈碱受体功能的结果。
In antigen-challenged guinea pigs there is recruitment of eosinophils into the lungs and to airway nerves, decreased function of inhibitory M-2 muscarinic autoreceptors on parasympathetic nerves in the lungs, and airway hyperresponsiveness. A rabbit antibody to guinea pig eosinophil major basic protein was used to determine whether M-2 muscarinic receptor dysfunction, and the subsequent hyperresponsiveness, are due to antagonism of the M-2 receptor by eosinophil major basic protein. Guinea pigs were sensitized, challenged with ovalbumin and hyperresponsiveness, and M-2 receptor function tested 24 h later with the muscarinic agonist pilocarpine. Antigen-challenged guinea pigs were hyperresponsive to electrical stimulation of the vagus nerves compared with controls. Likewise, loss of M-2 receptor function was demonstrated since the agonist pilocarpine inhibited vagally-induced bronchoconstriction in control but not challenged animals. Pretreatment with rabbit antibody to guinea pig eosinophil major basic protein prevented hyperresponsiveness, and protected Mt receptor function in the antigen-challenged animals without inhibiting eosinophil accumulation in the lungs or around the nerves. Thus, hyperresponsiveness is a result of inhibition of neuronal M-2 muscarinic receptor function by eosinophil major basic protein in antigen-challenged guinea pigs.