Halayko A J, Stephens N L
Department of Physiology, University of Manitoba, Winnipeg, Canada.
Can J Physiol Pharmacol. 1994 Nov;72(11):1448-57. doi: 10.1139/y94-209.
Asthma is considered to be a chronic inflammatory disease of the airways and is highlighted by excessive airway narrowing in response to various stimuli. Subepithelial fibrosis and increased airway smooth muscle mass are characteristic pathological features of the disease. Airway remodelling in asthma involves cellular hyperplasia and hypertrophy of bronchial myocytes. Smooth muscle cells from a variety of tissues have been shown to be multifunctional mesenchymal cells capable of expressing considerable phenotypic plasticity in vivo in response to injury and pathological stimuli. The growth response of vascular smooth muscle cells following arterial injury has been fairly well characterized, and it appears many of the chemical mediators responsible are common to the inflamed bronchi seen in asthmatics. Specific studies regarding the effects of phenotypic modulation of airway smooth muscle and the potential contribution of this phenomenon to the pathogenesis of chronic asthma have not been carried out. Limited evidence, some indirect, suggests that contractile properties of smooth muscle from inflamed tissues are altered; if this is the case in asthma, then considerations of the effects of airway smooth muscle hypertrophy should be broadened beyond that of only contributing to bronchial hyperresponsiveness via an increase in bronchial wall thickness. Recruitment and modulation of smooth muscle cells to functionally different phenotypes, which contribute to fibrosis by secreting extracellular matrix materials and promote cellular hyperplasia by producing growth factors, are known to occur in atherogenic blood vessels; and evidence suggests that airway smooth muscle cells might play a similar role in asthma. We report the identification of markers of differentiation for airway smooth muscle cells. These markers should be useful tools in the elucidation of phenotypic heterogeneity of smooth muscle in asthmatic airways and, thereby, allow for the definition of a clearer role for bronchial smooth muscle cells in the pathogenesis of chronic asthma.
哮喘被认为是一种气道慢性炎症性疾病，其特征是气道对各种刺激反应过度狭窄。上皮下纤维化和气道平滑肌质量增加是该疾病的典型病理特征。哮喘中的气道重塑涉及支气管肌细胞的细胞增生和肥大。来自多种组织的平滑肌细胞已被证明是多功能间充质细胞，能够在体内对损伤和病理刺激做出反应，表现出相当大的表型可塑性。动脉损伤后血管平滑肌细胞的生长反应已得到相当充分的表征，并且似乎许多负责的化学介质与哮喘患者发炎支气管中所见的介质相同。关于气道平滑肌表型调节的影响以及这种现象对慢性哮喘发病机制的潜在贡献的具体研究尚未开展。有限的证据（有些是间接的）表明，发炎组织中平滑肌的收缩特性发生了改变；如果哮喘中也是如此，那么对气道平滑肌肥大影响的考虑应扩大到不仅仅是通过增加支气管壁厚度导致支气管高反应性。已知在动脉粥样硬化血管中会发生平滑肌细胞募集和调节至功能不同的表型，这些表型通过分泌细胞外基质材料促进纤维化，并通过产生生长因子促进细胞增生；有证据表明气道平滑肌细胞在哮喘中可能起类似作用。我们报告了气道平滑肌细胞分化标志物的鉴定。这些标志物应有助于阐明哮喘气道中平滑肌的表型异质性，从而更清楚地界定支气管平滑肌细胞在慢性哮喘发病机制中的作用。
