Antibody to VLA-4, but not to L-selectin, protects neuronal M-2 muscarinic receptors in antigen-challenged guinea pig airways
Antibody to VLA-4, but not to L-selectin, protects neuronal M-2 muscarinic receptors in antigen-challenged guinea pig airways
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DOI：
10.1172/jci119372
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发表时间：
1997-04-15
影响因子：
15.9
通讯作者：
Bochner, BS
中科院分区：
文献类型：
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作者：
Fryer, AD;Costello, RW;Bochner, BS
致敏豚鼠的抗原攻击降低了抑制性 M-2 毒蕈碱自身受体对肺部副交感神经的功能，增强了迷走神经诱导的支气管收缩。 M-2 受体功能的丧失与气道神经周围嗜酸性粒细胞的积聚有关。为了确定通过表达 VLA-4 和 L-选择素来募集嗜酸性粒细胞是否对 M-2 受体功能丧失至关重要，用 VLA-4 (HP1/2) 或 L-选择素 (LAM1-116) 单克隆抗体对豚鼠进行预处理。用卵清蛋白对豚鼠进行致敏和攻击，并测试 M-2 受体功能。在对照组中，没食子胺对神经元 M-2 毒蕈碱受体的阻断增强了迷走神经诱导的支气管收缩，而在受攻击的动物中，这种效应显着降低，证实了 M-2 受体功能障碍。用 HP1/2（而非 LAM1-116）预处理可以保护抗原攻击动物中的 M-2 受体功能。 HP1/2 还抑制高反应性的发展，并选择性抑制肺部嗜酸性粒细胞的积累（通过灌洗和组织学检测）。因此，抑制嗜酸性粒细胞流入肺部可以保护 M-2 毒蕈碱受体的功能，从而防止抗原攻击的豚鼠出现高反应性。
Antigen challenge of sensitized guinea pigs decreases the function of inhibitory M-2 muscarinic autoreceptors on parasympathetic nerves in the lung, potentiating vagally induced bronchoconstriction. Loss of M-2 receptor function is associated with the accumulation of eosinophils around airway nerves. To determine whether recruitment of eosinophils via expression of VLA-4 and L-selectin is critical for loss of M-2 receptor function, guinea pigs were pretreated with monoclonal antibodies to VLA-4 (HP1/2) or L-selectin (LAM1-116). Guinea pigs were sensitized and challenged with ovalbumin, and M-2 receptor function was tested. In controls, blockade of neuronal M-2 muscarinic receptors by gallamine potentiated vagally induced bronchoconstriction, while in challenged animals this effect was markedly reduced, confirming M-2 receptor dysfunction. Pretreatment with HP1/2, but not with LAM1-116, protected M-2 receptor function in the antigen-challenged animals. HP1/2 also inhibited the development of hyperresponsiveness, and selectively inhibited accumulation of eosinophils in the lungs as measured by lavage and histology. Thus, inhibition of eosinophil influx into the lungs protects the function of M-2 muscarinic receptors, and in so doing, prevents hyperresponsiveness in antigen-challenged guinea pigs.