Ca2+-signaling in airway smooth muscle cells is altered in T-bet knock-out mice.
Ca2+-signaling in airway smooth muscle cells is altered in T-bet knock-out mice.
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DOI：
10.1186/1465-9921-7-33
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发表时间：
2006-02-23
影响因子：
5.8
通讯作者：
Huber RM
中科院分区：
文献类型：
--
作者：
Bergner A;Kellner J;Silva AK;Gamarra F;Huber RM
气道平滑肌细胞（ASMC）在支气管高反应性（BHR）中起关键作用。导致ASMC收缩的信号级联的主要组分是钙。到目前为止，激动剂诱导的钙离子信号在哮喘中的研究比较先天属性的近交系大鼠或小鼠品系，或通过使用选定的介质已知参与哮喘。T-bet基因敲除（KO）小鼠显示出过敏性哮喘的关键特征，如向TH 2淋巴细胞的转移，并显示出广谱的哮喘样组织学和功能特征。在这项研究中，我们的目的是调查是否钙稳态ASMC改变T-bet KO-小鼠作为哮喘的实验模型。从T-bet KO-和野生型小鼠中获得100 - 200 μm厚的肺切片。通过视频显微镜测量对乙酰胆碱（ACH）的气道收缩反应，并使用双光子显微镜评估单个肺切片ASMC中的Ca 2+信号。与野生型小鼠相比，来自T-bet KO小鼠的气道显示出增加的基线气道张力（BAT）和BHR。这可以通过将野生型小鼠的肺切片与IL-13孵育来模拟。BAT增加与细胞内Ca 2+浓度自发变化的发生率增加相关，而BHR与较高的ACH诱导的Ca 2+瞬变和ASMC显示Ca 2+振荡的比例增加相关。与野生型小鼠相比，使用咖啡因或cyclopiazonic酸排空细胞内Ca 2+商店诱导T-bet KO-ASMC中Ca 2+升高。ASMC的Ca 2+稳态改变有助于T-bet KO小鼠肺切片中BAT和BHR的增加，作为鼠哮喘模型。我们建议，更高的Ca 2+含量的细胞内Ca 2+商店参与这些变化的病理生理。
Airway smooth muscle cells (ASMC) play a key role in bronchial hyperresponsiveness (BHR). A major component of the signaling cascade leading to ASMC contraction is calcium. So far, agonist-induced Ca2+-signaling in asthma has been studied by comparing innate properties of inbred rat or mouse strains, or by using selected mediators known to be involved in asthma. T-bet knock-out (KO) mice show key features of allergic asthma such as a shift towards TH2-lymphocytes and display a broad spectrum of asthma-like histological and functional characteristics. In this study, we aimed at investigating whether Ca2+-homeostasis of ASMC is altered in T-bet KO-mice as an experimental model of asthma. Lung slices of 100 to 200 μm thickness were obtained from T-bet KO- and wild-type mice. Airway contraction in response to acetylcholine (ACH) was measured by video-microscopy and Ca2+-signaling in single ASMC of lung slices was assessed using two-photon-microscopy. Airways from T-bet KO-mice showed increased baseline airway tone (BAT) and BHR compared to wild-type mice. This could be mimicked by incubation of lung slices from wild-type mice with IL-13. The increased BAT was correlated with an increased incidence of spontaneous changes in intracellular Ca2+-concentrations, whereas BHR correlated with higher ACH-induced Ca2+-transients and an increased proportion of ASMC showing Ca2+-oscillations. Emptying intracellular Ca2+-stores using caffeine or cyclopiazonic acid induced higher Ca2+-elevations in ASMC from T-bet KO- compared to wild-type mice. Altered Ca2+-homeostasis of ASMC contributes to increased BAT and BHR in lung slices from T-bet KO-mice as a murine asthma model. We propose that a higher Ca2+-content of the intracellular Ca2+-stores is involved in the pathophysiology of these changes.
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5-HT，ACH和KCL诱导的钙振荡的频率决定了肺内支气管的平滑肌细胞的收缩。
影响因子：
3.8
作者：
Perez, Jose F;Sanderson, Michael J
通讯作者：
Sanderson, Michael J
DOI：
10.1152/ajplung.00043.2003
发表时间：
2003-12-01
影响因子：
4.9
作者：
Kuo, KH;Dai, JZ;van Breemen, C
通讯作者：
van Breemen, C
影响因子：
4
作者：
Prakash, YS;Pabelick, CM;Sieck, GC
通讯作者：
Sieck, GC
DOI：
10.1164/ajrccm.163.4.9911091
发表时间：
2001-03-01
影响因子：
24.7
作者：
Pype, JL;Xu, HY;Verleden, GM
通讯作者：
Verleden, GM
影响因子：
56.9
作者：
Finotto, S;Neurath, MF;Glimcher, LH
通讯作者：
Glimcher, LH