Kraneveld A D, Folkerts G, Van Oosterhout A J, Nijkamp F P
Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands.
Int J Immunopharmacol. 1997 Sep-Oct;19(9-10):517-27. doi: 10.1016/s0192-0561(97)00085-4.
Airway hyperreactivity to bronchoconstrictor mediators is a main characteristic in the majority of asthmatic patients and correlates well with the severity of the disease. The airways of asthmatic patients are characterized by an inflammatory state resulting in activation of lung tissue cells and attraction and infiltration of leukocytes from the blood. The accumulation of eosinophilic leukocytes is a prominent feature of inflammatory reactions that occurs in allergic asthma. The increase in number of eosinophils is important since it correlates in time with an increase in bronchial hyperresponsiveness. Viral respiratory infections can also induce eosinophilia and airway hyperresponsiveness in humans and animals and can worsen asthmatic reactions. This report reviews current opinions on the relationship between inflammation-induced eosinophil accumulation/activation and the development of airway hyperresponsiveness and the possible role for sensory neuropeptides in this process. Firstly, CC chemokines play an important role in allergic airway inflammation and respiratory viral infections leading to eosinophil recruitment. Secondly, it can be concluded that IL5 is involved in the development in airway hyperresponsiveness. IL5 has profound effects on eosinophils as promoter of growth, differentiation and proliferation, chemoattractant, activator and primer. However, it is conceivable that in animal models for allergic asthma besides IL5 other regulatory mediators may be involved in eosinophil migration and activation in the lung, which in turn will lead to airway hyperresponsiveness. Recent data support the possible role of eotaxin and its eosinophil-specific receptor CCR-3 in eosinophil chemotaxis and activation in allergic asthma. Moreover, it is suggested that the development of airway eosinophilia in vivo involves a two-step mechanism, elicited by eotaxin and IL5. The precise mechanism by which eosinophils induce bronchial hyperresponsiveness is at present unknown. Sensory neuropeptides could be important mediators in this process, since it has been demonstrated that airway nerves are surrounded by and infiltrated with eosinophils after antigen challenge. Sensory neuropeptides could be the final, more downstream, common pathway after eosinophil infiltration and activation in inducing airway hyperresponsiveness due to allergen inhalation or respiratory viral infections. In conclusion, in the process of the development of airway hyperresponsiveness observed during viral infections or in allergic asthma, the IL5/eotaxin-induced infiltration and activation of eosinophils in the airways is evident. Following this step, eosinophil-derived inflammatory mediators will induce the release of sensory neuropeptides (possibly NK2-receptor activating tachykinins) which in turn will lead to airway hyperresponsiveness.
气道对支气管收缩介质的高反应性是大多数哮喘患者的主要特征，且与疾病严重程度密切相关。哮喘患者的气道具有炎症状态的特征，导致肺组织细胞活化以及血液中白细胞的吸引和浸润。嗜酸性白细胞的积聚是过敏性哮喘中发生的炎症反应的一个突出特征。嗜酸性粒细胞数量的增加很重要，因为它与支气管高反应性的增加在时间上相关。病毒性呼吸道感染也可在人和动物中诱导嗜酸性粒细胞增多和气道高反应性，并可使哮喘反应恶化。本报告综述了目前关于炎症诱导的嗜酸性粒细胞积聚/活化与气道高反应性发展之间关系以及感觉神经肽在此过程中可能作用的观点。首先，CC趋化因子在过敏性气道炎症和导致嗜酸性粒细胞募集的呼吸道病毒感染中起重要作用。其次，可以得出结论，IL-5参与气道高反应性的发展。IL-5作为生长、分化和增殖的促进剂、趋化剂、激活剂和启动剂，对嗜酸性粒细胞有深远影响。然而，可以想象，在过敏性哮喘动物模型中，除了IL-5之外，其他调节介质可能参与肺中嗜酸性粒细胞的迁移和活化，这反过来又会导致气道高反应性。最近的数据支持嗜酸性粒细胞趋化因子及其嗜酸性粒细胞特异性受体CCR-3在过敏性哮喘中嗜酸性粒细胞趋化和活化中的可能作用。此外，有人提出体内气道嗜酸性粒细胞增多症的发展涉及由嗜酸性粒细胞趋化因子和IL-5引发的两步机制。嗜酸性粒细胞诱导支气管高反应性的确切机制目前尚不清楚。感觉神经肽可能是这一过程中的重要介质，因为已经证明抗原激发后气道神经被嗜酸性粒细胞包围并浸润。感觉神经肽可能是嗜酸性粒细胞浸润和活化后诱导因吸入变应原或呼吸道病毒感染导致气道高反应性的最终、更下游的共同途径。总之,在病毒感染或过敏性哮喘期间观察到的气道高反应性发展过程中，IL-5/嗜酸性粒细胞趋化因子诱导的气道嗜酸性粒细胞浸润和活化是明显的。在此步骤之后，嗜酸性粒细胞衍生的炎症介质将诱导感觉神经肽（可能为NK2受体激活速激肽）的释放，这反过来又会导致气道高反应性。
