CD4+ T cells enhance the unloaded shortening velocity of airway smooth muscle by altering the contractile protein expression.
CD4+ T cells enhance the unloaded shortening velocity of airway smooth muscle by altering the contractile protein expression.
复制标题
CD4 T 细胞通过改变收缩蛋白的表达来增强气道平滑肌的无负荷缩短速度。
DOI：
10.1113/jphysiol.2014.270843
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发表时间：
2014
期刊：
影响因子：
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通讯作者：
Lauzon,Anne-Marie
中科院分区：
文献类型：
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作者：
Matusovsky,OlegS;Nakada,EmilyM;Kachmar,Linda;Fixman,ElizabethD;Lauzon,Anne-Marie
激活的CD4+T细胞可增强气道平滑肌的收缩力。为了增强收缩性，需要CD4+T细胞与平滑肌之间的接触。收缩力的增强与快速肌球蛋白异构体水平的增加有关。我们的数据表明，在气道高反应性和哮喘中，炎症细胞促进气道平滑肌过度收缩。大量数据表明过敏性气道疾病的发病机制是由异常的T -辅助性2 （Th2）炎症反应策划的。在人类哮喘患者和变应性气道疾病的啮齿动物模型中，CD4+T细胞已经定位于气道平滑肌（ASM），它们与ASM的增殖反应有关。CD4+T细胞是否也改变了ASM的收缩性尚未得到解决。我们建立了一个蛋白体外系统来评估抗原刺激的CD4+T细胞改变布朗挪威大鼠气管肌肉收缩反应的能力。我们的数据表明，在抗原刺激的CD4+T细胞共孵育24小时后，ASM的空载缩短速度（Vmax）显著增加，而应激没有改变。增强的vmax依赖于CD4+T细胞与ASM之间的接触，并与快速（+）插入平滑肌肌球蛋白重链异构体水平的增加相关。肌球蛋白轻链激酶和肌球蛋白轻链磷酸化水平也增加。力学和收缩蛋白水平的变化是短暂的，在共孵育48小时后，两者都下降到控制水平。当几种炎症细胞和介质相互作用或经过反复的抗原挑战后，肌肉表型可能会发生更永久的改变。进一步的研究将等待新的组织培养方法，以在更长的时间内保持肌肉的特性。总之，我们的数据表明炎症细胞促进气道高反应性和哮喘的ASM过度收缩。
Key pointsActivated CD4+T cells enhance the contractility of airway smooth muscle.In order to enhance contractility, contact between CD4+T cells and smooth muscle is required.The enhanced contractility is correlated with increased levels of fast myosin isoform.Our data suggest that inflammatory cells promote airway smooth muscle hypercontractility in airway hyper‐responsiveness and asthma.AbstractAbundant data indicate that pathogenesis in allergic airways disease is orchestrated by an aberrant T‐helper 2 (Th2) inflammatory response. CD4+T cells have been localized to airway smooth muscle (ASM) in both human asthmatics and in rodent models of allergic airways disease, where they have been implicated in proliferative responses of ASM. Whether CD4+T cells also alter ASM contractility has not been addressed. We established anin vitrosystem to assess the ability of antigen‐stimulated CD4+T cells to modify contractile responses of the Brown Norway rat trachealis muscle. Our data demonstrated that the unloaded velocity of shortening (Vmax) of ASM was significantly increased upon 24 h co‐incubation with antigen‐stimulated CD4+T cells, while stress did not change. EnhancedVmaxwas dependent upon contact between the CD4+T cells and the ASM and correlated with increased levels of the fast (+)insert smooth muscle myosin heavy chain isoform. The levels of myosin light chain kinase and myosin light chain phosphorylation were also increased within the muscle. The alterations in mechanics and in the levels of contractile proteins were transient, both declining to control levels after 48 h of co‐incubation. More permanent alterations in muscle phenotype might be attainable when several inflammatory cells and mediators interact together or after repeated antigenic challenges. Further studies will await new tissue culture methodologies that preserve the muscle properties over longer periods of time. In conclusion, our data suggest that inflammatory cells promote ASM hypercontractility in airway hyper‐responsiveness and asthma.