Hirst S J
Department of Respiratory Medicine and Allergy, The Guy's, King's and St Thomas' School of Medicine, Guy's Hospital, King's College London, London, UK.
Clin Exp Allergy. 2000 Jun;30 Suppl 1:54-9.
Traditionally, the contractile properties of airway smooth muscle have been regarded as its sole contribution to the pathogenesis of asthma. However, our understanding of the role that this structural cell plays in asthma is changing. Airway smooth muscle can undergo hyperplasia and/or hypertrophy leading to structural changes in the airway wall which contribute to the development of persistent airway obstruction and increased non-specific airway hyperresponsiveness in chronic severe asthma. Many studies in vitro have characterized airway smooth muscle proliferation induced by various pro-inflammatory mediators, growth factors and components of the extracellular matrix, but the mediator(s) responsible for the observed increase in airway wall smooth muscle content in vivo remain to be determined. In addition to geometric obstruction by increased airway wall thickening, proliferating airway smooth muscle cells undergo phenotypic modulation from a contractile to synthetic-proliferative state where additional functions of airway smooth muscle such as cytokine/chemokine and extracellular matrix secretion may become more apparent. This may be especially relevant in the diseased airway where the content of airway smooth muscle as a fraction of the total cells present in the airway wall is already increased. Airway smooth muscle cells may also interact by direct contact with immunocytes such as T lymphocytes through expression of cell adhesion molecules with the result that myocyte DNA synthesis is induced. As additional functions of airway smooth muscle are described, a more contemporary view is emerging that airway smooth cells may adopt an immuno-effector role in chronic asthma by proliferating, secreting cytokines, expressing adhesion molecules and by interacting with various inflammatory cells. This may involve changes in the phenotypic status of airway smooth muscle, and as a result, these cells may play an active role in perpetuating and orchestrating airway inflammation in the remodelled airway. An important phase for future airway smooth muscle research will be to determine the extent that these putative mechanisms exist in vivo in the pathogenesis of chronic severe asthma.
传统上，气道平滑肌的收缩特性被认为是其在哮喘发病机制中的唯一作用。然而，我们对这种结构细胞在哮喘中所起作用的理解正在发生变化。气道平滑肌可发生增生和/或肥大，导致气道壁结构改变，这有助于慢性重度哮喘中持续性气道阻塞的发展和非特异性气道高反应性的增加。许多体外研究已经对各种促炎介质、生长因子和细胞外基质成分诱导的气道平滑肌增殖进行了表征，但体内导致气道壁平滑肌含量增加的介质仍有待确定。除了气道壁增厚导致的几何性阻塞外，增殖的气道平滑肌细胞会经历从收缩状态到合成-增殖状态的表型调节，在此状态下，气道平滑肌的其他功能，如细胞因子/趋化因子分泌和细胞外基质分泌可能会更加明显。这在患病气道中可能尤为重要，因为气道平滑肌作为气道壁中存在的总细胞的一部分，其含量已经增加。气道平滑肌细胞还可能通过细胞粘附分子的表达与免疫细胞如T淋巴细胞直接接触相互作用，从而诱导肌细胞DNA合成。随着气道平滑肌其他功能的描述，一种更现代的观点正在出现，即气道平滑肌细胞可能通过增殖、分泌细胞因子、表达粘附分子以及与各种炎症细胞相互作用，在慢性哮喘中发挥免疫效应作用。这可能涉及气道平滑肌表型状态的变化，因此，这些细胞可能在重塑气道中使气道炎症持续并协调气道炎症方面发挥积极作用。未来气道平滑肌研究的一个重要阶段将是确定这些假定机制在慢性重度哮喘发病机制中在体内存在的程度。
