Real-time imaging of asthmatic epithelial cells identifies migratory deficiencies under type-2 conditions.
Real-time imaging of asthmatic epithelial cells identifies migratory deficiencies under type-2 conditions.
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DOI：
10.1016/j.jaci.2021.08.027
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Wenzel SE
中科院分区：
文献类型：
--
作者：
Jin M;Watkins S;Larriba Y;Wallace C;St Croix C;Zhou X;Zhao J;Peddada S;Wenzel SE
上皮细胞越来越被认为是哮喘及其表型的病理贡献者。虽然哮喘上皮细胞延迟伤口闭合一直被观察到，但其潜在机制仍然知之甚少，部分原因是难以研究涉及极化多层细胞系统的动态生理过程。虽然2型免疫已经被认为发挥了作用，但修复减弱的机制尚不清楚。开发和利用来自哮喘患者的原代多层极化上皮细胞系统，以评估2型和未治疗条件下对创伤的细胞迁移反应。在IL-13和未处理的条件下评价了用于多层极化细胞的新型创伤装置，沿着延时活细胞/实时共聚焦成像。抑制2型酶，15脂氧合酶（15 LO 1），对该过程的影响也得到了解决。通过高维调频莫比乌斯分析细胞迁移模式以进行统计学比较。IL-13刺激通过改变单个细胞的总速度、方向性和加速度对伤口愈合产生负面影响。抑制15 LO 1通过提高总速度而部分改善创伤修复。迁移异常导致IL-13处理的细胞的伤口闭合明显较慢，这被15 LO 1抑制适度逆转，表明其作为哮喘治疗靶点的潜力。这些新的方法提供了新的方法来动态研究细胞运动和识别病理过程。IL-13通过延迟迁移模式减少AEC的伤口修复。15 LO 1抑制部分恢复延迟的伤口修复。利用先进的实时共聚焦技术和先进的统计方法，本文确定了在2型/IL-13免疫条件下哮喘气道上皮细胞（AEC）的伤口修复和迁移模式的显着异常。
The epithelium is increasingly recognized as a pathologic contributor to asthma and its phenotypes. Although delayed wound closure by asthmatic epithelial cells is consistently observed, underlying mechanisms remain poorly understood, partly due to difficulties in studying dynamic physiologic processes involving polarized multilayered cell systems. Although Type-2 immunity has been suggested to play a role, the mechanisms by which repair is diminished are unclear. To develop and utilize primary multilayered polarized epithelial cell systems, derived from asthmatic patients, to evaluate cell migration in response to wounding under Type-2 and untreated conditions. A novel wounding device for multilayered polarized cells, along with time-lapse live cell/real-time confocal imaging were evaluated under IL-13 and untreated conditions. The influence of inhibition of the Type-2 enzyme, 15 lipoxygenase (15LO1), on the process was also addressed. Cell migration patterns were analyzed by high dimensional Frequency Modulated Möbius for statistical comparisons. IL-13 stimulation negatively impacts wound healing by altering the Total speed, directionality and acceleration of individual cells. Inhibition 15LO1 partially improved the wound repair through improving Total speed. Migration abnormalities contributed to markedly slower wound closure of IL-13 treated cells, which was modestly reversed by 15LO1 inhibition, suggesting its potential as an asthma therapeutic target. These novel methodologies offer new ways to dynamically study cell movements and identify contributing pathologic processes. IL-13 decreases AECs wound repair by delaying migration patterns. 15LO1 inhibition partially recovers the delayed wound repair. Using cutting-edge real-time confocal technology and advanced statistical methods, this article identified marked abnormalities in the wound repair and migratory patterns of asthmatic airway epithelial cells (AECs) under Type-2/IL-13 immune conditions.
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影响因子：
6.1
作者：
Looi, K.;Buckley, A. G.;Stick, S. M.
通讯作者：
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影响因子：
8
作者：
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DOI：
10.1164/rccm.200907-1071oc
发表时间：
2010-05-01
影响因子：
24.7
作者：
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通讯作者：
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通讯作者：
Park JA
影响因子：
14.2
作者：
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通讯作者：
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