Synthetic responses in airway smooth muscle.
Synthetic responses in airway smooth muscle.
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DOI：
10.1016/j.jaci.2004.04.041
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发表时间：
2004-08-01
期刊：
影响因子：
--
通讯作者：
Johnson, Malcolm
中科院分区：
文献类型：
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作者：
Howarth, Peter H;Knox, Alan J;Johnson, Malcolm
人气道平滑肌（ASM）具有一些与哮喘发病有关的特性和功能，其合成能力正受到越来越多的关注。ASM能促进间质细胞外基质的形成，在这方面，哮喘组ASM与正常组相比，在定性和定量上都有不同的反应。因此，ASM细胞是重要的调节细胞，可能有助于哮喘细胞外基质内已知的改变。此外，通过整合素导向的信号传导，细胞外基质成分可以改变ASM细胞的增殖、存活和细胞骨架合成功能。ASM还具有丰富的生物活性趋化因子和细胞因子的功能，这些趋化因子和细胞因子能够通过促进气道环境中炎症细胞的募集、激活和运输，使哮喘和慢性阻塞性肺疾病的气道炎症持续存在。新出现的证据表明，气道重塑也可能是分泌炎性介质自分泌作用的结果，包括T(H)2细胞因子、生长因子和cox -2依赖性前列腺素。最后，ASM细胞含有β(2)-肾上腺素能受体和糖皮质激素受体，可能是β(2)-肾上腺素能受体激动剂/皮质类固醇相互作用的关键靶点。长效β(2)激动剂和皮质类固醇联合使用在抑制炎症介质释放和ASM细胞的迁移和增殖方面似乎具有附加和/或协同作用。
Human airway smooth muscle (ASM) has several properties and functions that contribute to asthma pathogenesis, and increasing attention is being paid to its synthetic capabilities. ASM can promote the formation of the interstitial extracellular matrix, and in this respect, ASM from asthmatic subjects compared with normal subjects responds differently, both qualitatively and quantitatively. Thus, ASM cells are important regulating cells that potentially contribute to the known alterations within the extracellular matrix in asthma. In addition, through integrin-directed signaling, extracellular matrix components can alter the proliferative, survival, and cytoskeletal synthetic function of ASM cells. ASM also functions as a rich source of biologically active chemokines and cytokines that are capable of perpetuating airway inflammation in asthma and chronic obstructive pulmonary disease by promoting recruitment, activation, and trafficking of inflammatory cells in the airway milieu. Emerging evidence shows that airway remodeling may also be a result of the autocrine action of secreted inflammatory mediators, including T(H)2 cytokines, growth factors, and COX-2-dependent prostanoids. Finally, ASM cells contain both beta(2)-adrenergic receptors and glucocorticoid receptors and may represent a key target for beta(2)-adrenergic receptor agonist/corticosteroid interactions. Combinations of long-acting beta(2)-agonists and corticosteroids appear to have additive and/or synergistic effects in inhibiting inflammatory mediator release and the migration and proliferation of ASM cells.