University of Pennsylvania Medical Center, Pulmonary, Allergy and Critical Care Division, Department of Medicine, BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104, USA.
Expert Rev Clin Immunol. 2006 May;2(3):353-64. doi: 10.1586/1744666X.2.3.353.
There is growing evidence indicating the existence of a causal relationship between abnormal airway smooth muscle (ASM) function and airway hyper-responsiveness, a poorly understood feature of asthma that can be defined as an excessive bronchospastic response. In recent years, there has been a veritable explosion of articles suggesting that ASM exposed to proasthmatic cytokines can elicit a hyper-responsive state to contractile G-protein-coupled receptor (GPCR) agonists. Aberrant airway responsiveness could result from abnormal calcium signaling, with changes occurring at various levels of GPCR-associated signal transduction. This review presents the latest observations describing novel mechanistic models that could explain the involvement of ASM in airway hyper-responsiveness. This review will discuss the role of ASM in beta(2)-agonist-mediated bronchial hyper-responsiveness and the clinical significance of cell-cell contact between ASM and mast cells recently described to be intimately infiltrated within the ASM tissues in asthmatic patients. The possibility that allergens could trigger airway hyper-responsiveness by directly acting on ASM via activation of immunoglobulin E receptors, FcepsilonRI and FCepsilonRII will also be discussed. These important findings further support the notion that targeting ASM could offer new treatment for many features of asthma, including airway hyper-responsiveness. Future therapeutic intervention includes: the prevention of ASM-inflammatory cell physical and/or functional interaction, the inhibition of Immunoglobulin E receptor-dependent signal transduction, and the abrogation of cytokine-dependent pathways that modulate receptor-associated calcium metabolism.
越来越多的证据表明，气道平滑肌（ASM）功能异常与气道高反应性之间存在因果关系，气道高反应性是哮喘的一个尚未完全了解的特征，可以定义为过度的支气管痉挛反应。近年来，有大量文章表明，暴露于促哮喘细胞因子的 ASM 可以引发对收缩性 G 蛋白偶联受体（GPCR）激动剂的高反应状态。气道反应性异常可能源于异常的钙信号，这种变化发生在 GPCR 相关信号转导的各个水平。这篇综述介绍了最新的观察结果，描述了可以解释 ASM 参与气道高反应性的新机制模型。这篇综述将讨论 ASM 在β2-激动剂介导的支气管高反应性中的作用，以及最近在哮喘患者的 ASM 组织中发现的 ASM 与肥大细胞之间细胞-细胞接触的临床意义。变应原可能通过激活免疫球蛋白 E 受体（FcεRI 和 FCεRII）直接作用于 ASM 而引发气道高反应性的可能性也将被讨论。这些重要发现进一步支持了这样一种观点，即靶向 ASM 可能为哮喘的许多特征，包括气道高反应性，提供新的治疗方法。未来的治疗干预包括：预防 ASM-炎症细胞的物理和/或功能相互作用，抑制免疫球蛋白 E 受体依赖性信号转导，以及阻断调节受体相关钙代谢的细胞因子依赖性途径。
