Hyperacidity of secreted fluid from submucosal glands in early cystic fibrosis
Hyperacidity of secreted fluid from submucosal glands in early cystic fibrosis
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DOI：
10.1152/ajpcell.00379.2005
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发表时间：
2006-03-01
影响因子：
5.5
通讯作者：
Verkman, AS
中科院分区：
文献类型：
--
作者：
Song, YL;Salinas, D;Verkman, AS
先前的研究表明，囊性纤维化（CF）患者气道粘膜下腺体的液体分泌物减少和高粘性，可能有助于CF气道疾病的发病机制。由于CF跨膜传导调节因子（CFTR）蛋白可以转运氯离子和碳酸氢根，我们使用患有轻微CF肺病的儿科受试者的鼻活检来研究早期CF中的腺液pH值是否异常。在BCECF-dextran油染色下测量的新鲜分泌液滴的腺液pH值，在6名CF受试者的活检组织中为6.57 +/- 0.09（平均值+/- SE），显著低于8名非CF活检组织中的7.18 +/- 0.06（P < 0.01）。为了排除CF中明显的腺液胃酸过多是由气道表面改变液体pH值引起的可能性，使用微插管法测量离开腺孔的液体中的pH值。在猪气管和人支气管中，CFTR抑制剂可使腺液pH值降低0.45单位，但阿米洛利不影响腺液pH值。通过沉积在油覆盖的气道表面上的300 nl液滴的pH值变化来研究猪气管表面上皮的酸碱转运。液滴具有特定的离子组成/pH和/或含有转运蛋白激活剂/抑制剂。我们发现了CFTR依赖性的气管表面上皮细胞的碳酸氢盐转运以及ATP/组胺刺激的质子分泌的证据，但没有钠/质子或氯/碳酸氢盐交换。这些结果提供了CF腺体分泌物中固有的胃酸过多的证据，这可能有助于CF气道病理学。
Prior studies have shown that fluid secretions from airway submucosal glands in cystic fibrosis (CF) are reduced and hyperviscous, possibly contributing to the pathogenesis of CF airway disease. Because the CF transmembrane conductance regulator (CFTR) protein can transport both chloride and bicarbonate, we investigated whether gland fluid pH is abnormal in early CF, using nasal biopsies from pediatric subjects having minimal CF lung disease. Gland fluid pH, measured in freshly secreted droplets under oil stained with BCECF-dextran, was 6.57 +/- 0.09 ( mean +/- SE) in biopsies from six CF subjects, significantly lower than 7.18 +/- 0.06 in eight non-CF biopsies (P < 0.01). To rule out the possibility that the apparent gland fluid hyperacidity in CF results from modification of fluid pH by the airway surface, a microcannulation method was used to measure pH in fluid exiting gland orifices. In pig trachea and human bronchi, gland fluid pH was reduced by up to 0.45 units by CFTR inhibitors, but was not affected by amiloride. Acid base transport in the surface epithelium of pig trachea was studied from pH changes in 300-nl fluid droplets deposited onto the oil-covered airway surface. The droplets had specified ionic composition/pH and/or contained transporter activators/inhibitors. We found evidence for CFTR-dependent bicarbonate transport by the tracheal surface epithelium as well as ATP/histamine-stimulated proton secretion, but not for sodium/proton or chloride/bicarbonate exchange. These results provide evidence for intrinsic hyperacidity in CF gland fluid secretions, which may contribute to CF airway pathology.