Involvement of tachykinin NK1 receptor in the development of allergen-induced airway hyperreactivity and airway inflammation in conscious, unrestrained guinea pigs
Involvement of tachykinin NK1 receptor in the development of allergen-induced airway hyperreactivity and airway inflammation in conscious, unrestrained guinea pigs
复制标题
DOI：
10.1164/ajrccm.159.2.9804125
复制
发表时间：
1999-02-01
影响因子：
24.7
通讯作者：
Meurs, H
中科院分区：
文献类型：
--
作者：
Schuiling, M;Zuidhof, AB;Meurs, H
有研究表明，速激肽NK1受体介导的以微血管渗漏、黏液分泌、呼吸道炎症细胞浸润和活化为特征的神经源性炎症可能参与了过敏性哮喘的发病过程。因此，在过敏性哮喘的豚鼠模型中，我们使用选择性非肽NK1受体拮抗剂SR140333，研究了NK1受体在变应原诱导的早期(EAR)和晚期(LAR)哮喘反应、反应后的气道高反应性(AHR)和呼吸道炎症中的作用。在两个不同的场合，间隔1wk，随机交换设计，在OA刺激前30min和之后5.5h(耳与LAR之间)分别吸入生理盐水(3min)或SR140333(100 nM，3min)。对照组在两次骨关节炎刺激前和刺激后5.5小时分别吸入生理盐水。与生理盐水对照组吸入相比，SR140333对耳部和LAR均无显著影响。然而，NK1受体拮抗剂显著降低了OA刺激后5h耳部的组胺反应性(组胺反应性增加1.77+/-0.13倍，对照组为2.50+/-0.25倍，p<；0.01)，以及OA攻击后23h的LAR(分别为1.15+/-0.12倍和1.98+/-0.34倍，p<；0.05)。此外，在第二次OA刺激后25小时进行的支气管肺泡破坏研究表明，SR140333显著抑制变应原诱导的嗜酸性粒细胞、中性粒细胞和淋巴细胞在呼吸道中的渗透(p<；0.05)，而减少纤毛上皮细胞在气道腔中的聚集(p=0.10)。这些结果表明，NK1受体参与了过敏原诱导的AHR向组胺转化的过程，NK1受体介导的炎症细胞在呼吸道的浸润可能参与了这种AHR的形成。
It has been suggested that tachykinin NK1 receptor-mediated neurogenic inflammation, characterized by microvascular leakage, mucus secretion, and infiltration and activation of inflammatory cells in the airways, may be involved in allergic asthma. Therefore, in a guinea pig model of allergic asthma, we investigated the involvement of the NK1 receptor in allergen-induced early (EAR) and late (LAR) asthmatic reactions, airway hyperreactivity (AHR) after these reactions and airway inflammation, using the selective nonpeptide NK1 receptor antagonist SR140333. On two different occasions, separated by 1 wk interval, OA-sensitized guinea pigs inhaled either saline (3 min) or SR140333 (100 nM, 3 min) at 30 min before as well as at 5.5 h after OA provocation (between the EAR and LAR) in a random crossover design. A control group, receiving saline inhalations before and at 5.5 h after the two OA provocations, was included as well. SR140333 had no significant effect on either the EAR or the LAR compared with saline control inhalations. However, the NK1 receptor antagonist significantly reduced the OA-induced AHR to histamine, both after the EAR at 5 h after OA challenge (1.77+/- 0.13-fold increase in histamine reactivity versus 2.50 +/- 0.25-fold increase in the control animals, p < 0.01) and after the LAR at 23 h after OA challenge (1.15 +/- 0.12-fold increase versus 1.98 +/- 0.34-fold increase, respectively, p < 0.05). Moreover, bronchoalveolar ravage studies performed at 25 h after the second OA provocation indicated that SR140333 significantly inhibited the allergen-induced infiltration of eosinophils, neutrophils, and lymphocytes in the airways (p < 0.05 for all observations), whereas a tendency to reduced accumulation of ciliated epithelial cells in the airway lumen was observed (p = 0.10). These results indicate that the NK1 receptor is involved in the development of allergen-induced AHR to histamine, and that NK1 receptor-mediated infiltration of inflammatory cells in the airways may contribute to this AHR.