Baseline Goblet Cell Mucin Secretion in the Airways Exceeds Stimulated Secretion over Extended Time Periods, and Is Sensitive to Shear Stress and Intracellular Mucin Stores.
Baseline Goblet Cell Mucin Secretion in the Airways Exceeds Stimulated Secretion over Extended Time Periods, and Is Sensitive to Shear Stress and Intracellular Mucin Stores.
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DOI：
10.1371/journal.pone.0127267
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Davis CW
中科院分区：
文献类型：
--
作者：
Zhu Y;Abdullah LH;Doyle SP;Nguyen K;Ribeiro CM;Vasquez PA;Forest MG;Lethem MI;Dickey BF;Davis CW
气道粘蛋白分泌研究主要集中于杯状细胞对外源激动剂的反应，几乎排除了基线粘蛋白分泌（BLMS）。在人支气管上皮细胞培养物 (HBECC) 中，一小时内测量的最大激动剂刺激分泌超过基线约 3 倍，但粘蛋白储存完全排出，需要 24 小时才能完全恢复。因此，在 24 小时内，总基线超过激动剂诱导的分泌数倍。对 HBECC 和小鼠气管的研究表明 BLMS 对机械应力高度敏感。用 HBECC 收获三个连续 1 小时基线管腔孵育，产生相同的 BLMS 率；然而，将中间期延长至 72 小时显着降低了各自的速率，表明通过温和清洗 HBECC 管腔表面来刺激 BLMS。清洗 HBECC 后（t1/2 = 2.75 小时），BLMS 呈指数下降，直至接近于零。当流量跃升 5 倍时，暴露于低灌注率的 HBECC 表现出 BLMS 的尖峰状增加：BLMS 增加 >4 倍，然后在 5 分钟内下降至稳定平台，比对照高 1.5-2 倍。较高的流量跳跃会相应地导致较高的 BLMS 增加。诱导 HBECC 中的粘液增生会增加粘蛋白的产生、BLMS 和激动剂诱导的分泌。灌注期间小鼠气管 BLMS 比停止流动时高约 6 倍。 Munc13-2 null 小鼠气管由于细胞粘蛋白积累的缺陷而表现出与 WT 相似的 BLMS，这与较低值的预测相反。用 IL-13 在 WT 和 Munc13-2 null 气管中诱导的分级粘液化生导致 BLMS 成比例增加，表明初始 Munc13-2 小鼠 BLMS 因粘蛋白储备增加而升高。我们得出的结论是，BLMS 是，[i] 肺部粘蛋白分泌的主要组成部分，[ii] 由动态肺的机械活动维持，[iii] 与粘蛋白储存水平成正比，并且 [iv] 与激动剂诱导的粘蛋白分泌进行差异调节。
Airway mucin secretion studies have focused on goblet cell responses to exogenous agonists almost to the exclusion of baseline mucin secretion (BLMS). In human bronchial epithelial cell cultures (HBECCs), maximal agonist-stimulated secretion exceeds baseline by ~3-fold as measured over hour-long periods, but mucin stores are discharged completely and require 24 h for full restoration. Hence, over 24 h, total baseline exceeds agonist-induced secretion by several-fold. Studies with HBECCs and mouse tracheas showed that BLMS is highly sensitive to mechanical stresses. Harvesting three consecutive 1 h baseline luminal incubations with HBECCs yielded equal rates of BLMS; however, lengthening the middle period to 72 h decreased the respective rate significantly, suggesting a stimulation of BLMS by the gentle washes of HBECC luminal surfaces. BLMS declined exponentially after washing HBECCs (t1/2 = 2.75 h), to rates approaching zero. HBECCs exposed to low perfusion rates exhibited spike-like increases in BLMS when flow was jumped 5-fold: BLMS increased >4 fold, then decreased within 5 min to a stable plateau at 1.5–2-fold over control. Higher flow jumps induced proportionally higher BLMS increases. Inducing mucous hyperplasia in HBECCs increased mucin production, BLMS and agonist-induced secretion. Mouse tracheal BLMS was ~6-fold higher during perfusion, than when flow was stopped. Munc13-2 null mouse tracheas, with their defect of accumulated cellular mucins, exhibited similar BLMS as WT, contrary to predictions of lower values. Graded mucous metaplasia induced in WT and Munc13-2 null tracheas with IL-13, caused proportional increases in BLMS, suggesting that naïve Munc13-2 mouse BLMS is elevated by increased mucin stores. We conclude that BLMS is, [i] a major component of mucin secretion in the lung, [ii] sustained by the mechanical activity of a dynamic lung, [iii] proportional to levels of mucin stores, and [iv] regulated differentially from agonist-induced mucin secretion.
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DOI：
10.1152/ajplung.00410.2002
发表时间：
2003-06-01
影响因子：
4.9
作者：
Conway, JD;Bartolotta, T;Davis, CW
通讯作者：
Davis, CW
影响因子：
5.5
作者：
Ehre, Camille;Zhu, Yunxiang;Davis, C. William
通讯作者：
Davis, C. William
影响因子：
5.5
作者：
Grygorczyk, Ryszard;Furuya, Kishio;Sokabe, Masahiro
通讯作者：
Sokabe, Masahiro
影响因子：
5.2
作者：
Adler KB;Tuvim MJ;Dickey BF
通讯作者：
Dickey BF
DOI：
10.1056/nejmra0910061
发表时间：
2010-12-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Fahy JV;Dickey BF
通讯作者：
Dickey BF