Submucosal glands and airway defense.
Submucosal glands and airway defense.
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DOI：
10.1513/pats.2306015
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发表时间：
2004-01-01
期刊：
影响因子：
--
通讯作者：
Joo, Nam Soo
中科院分区：
文献类型：
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作者：
Wine, Jeffrey J;Joo, Nam Soo
大多数气道粘液是由粘膜下腺体响应神经信号产生的。腺体粘液捕获微生物，抑制它们的复制，并将它们从气道中清除。在囊性纤维化中，粘液清除受到损害，允许病原体在静态粘液中持续存在。这些触发炎症细胞的流入，但炎症的最佳效果，特别是其解决方案，还需要有效的粘液清除。我们的目的是了解囊性纤维化中粘液清除缺陷的基础。我们发现，在囊性纤维化的受试者中，粘膜下腺体分泌物对升高细胞内环AMP水平的药物的反应完全丧失，并且通过升高细胞内Ca2+水平刺激的粘液更厚。我们假设腺浆细胞功能性囊性纤维化跨膜传导调节因子的丧失使它们不能分泌阴离子和液体以响应任何刺激，导致可以拴系到腺导管的增厚的腺粘液。在原发性纤毛运动障碍中，粘液是正常的，但衬在腺管上的纤毛功能障碍也可能导致粘液从腺体中的清除不足。因此，在每种疾病的肺病理学的理解可能需要一个更好的了解腺体的结构和功能被添加到我们快速增长的了解表面上皮细胞。
Most airway mucus is produced by submucosal glands in response to neural signals. Gland mucus traps microbes, inhibits their replication, and clears them from the airways. In cystic fibrosis mucus clearance is compromised, allowing pathogens to persist in static mucus. These trigger an influx of inflammatory cells, but optimal effectiveness of inflammation, and especially its resolution, also requires effective mucus clearance. Our objective is to understand the basis for defective mucus clearance in cystic fibrosis. We discovered that in subjects with cystic fibrosis, submucosal gland secretion in response to agents that elevate intracellular cyclic AMP level is completely lost and mucus stimulated by elevating intracellular Ca2+ level is thicker. We hypothesize that loss of functional cystic fibrosis transmembrane conductance regulator from gland serous cells renders them unable to secrete anions and fluid in response to any stimulus, resulting in thickened gland mucus that can be tethered to the gland ducts. In primary ciliary dyskinesias, mucus is normal, but the dysfunctional cilia lining the gland ducts may also lead to inadequate clearance of mucus from glands. Thus, understanding of lung pathology in each disease may require that an improved understanding of gland structure and function be added to our rapidly growing understanding of surface epithelia.