Wang Xiaofei, Lytle Christian, Quinton Paul M
Dept, Pediatrics, Medical School, University of California, San Diego, San Diego, CA USA.
Respir Res. 2005 Jan 17;6(1):7. doi: 10.1186/1465-9921-6-7.
The pathological hallmarks of chronic obstructive pulmonary disease (COPD) are inflammation of the small airways (bronchiolitis) and destruction of lung parenchyma (emphysema). These forms of disease arise from chronic prolonged infections, which are usually never present in the normal lung. Despite the fact that primary hygiene and defense of the airways presumably requires a well controlled fluid environment on the surface of the bronchiolar airway, very little is known of the fluid and electrolyte transport properties of airways of less than a few mm diameter.
We introduce a novel approach to examine some of these properties in a preparation of minimally traumatized porcine bronchioles of about 1 mm diameter by microperfusing the intact bronchiole.
In bilateral isotonic NaCl Ringer solutions, the spontaneous transepithelial potential (TEP; lumen to bath) of the bronchiole was small (mean +/- sem: -3 +/- 1 mV; n = 25), but when gluconate replaced luminal Cl-, the bionic Cl- diffusion potentials (-58 +/- 3 mV; n = 25) were as large as -90 mV. TEP diffusion potentials from 2:1 NaCl dilution showed that epithelial Cl- permeability was at least 5 times greater than Na+ permeability. The anion selectivity sequence was similar to that of CFTR. The bionic TEP became more electronegative with stimulation by luminal forskolin (5 microM)+IBMX (100 microM), ATP (100 microM), or adenosine (100 microM), but not by ionomycin. The TEP was partially inhibited by NPPB (100 microM), GlyH-101* (5-50 microM), and CFTRInh-172* (5 microM). RT-PCR gave identifying products for CFTR, alpha-, beta-, and gamma-ENaC and NKCC1. Antibodies to CFTR localized specifically to the epithelial cells lining the lumen of the small airways.
These results indicate that the small airway of the pig is characterized by a constitutively active Cl- conductance that is most likely due to CFTR.
慢性阻塞性肺疾病（COPD）的病理特征是小气道炎症（细支气管炎）和肺实质破坏（肺气肿）。这些疾病形式源于慢性长期感染，而正常肺中通常不存在这种感染。尽管气道的初级卫生和防御可能需要细支气管气道表面有良好控制的液体环境，但对于直径小于几毫米的气道的液体和电解质转运特性知之甚少。
我们引入了一种新方法，通过对完整的约1毫米直径的猪细支气管进行微量灌注，来研究其中的一些特性。
在双侧等渗氯化钠林格液中，细支气管的自发跨上皮电位（TEP；管腔到浴液）很小（平均值±标准误：-3±1 mV；n = 25），但当葡萄糖酸盐替代管腔中的Cl-时，模拟的Cl-扩散电位（-58±3 mV；n = 25）高达-90 mV。2:1氯化钠稀释产生的TEP扩散电位表明，上皮细胞的Cl-通透性至少比Na+通透性大5倍。阴离子选择性序列与囊性纤维化跨膜传导调节因子（CFTR）相似。管腔中用福斯可林（5 microM）+异丁基甲基黄嘌呤（IBMX，100 microM）、ATP（100 microM）或腺苷（100 microM）刺激时，模拟的TEP变得更具负电性，但用离子霉素刺激则不然。TEP被5-硝基-2-（3-苯丙氨基）苯甲酸（NPPB，100 microM）、GlyH-101*（5 - 50 microM）和CFTRInh-172*（5 microM）部分抑制。逆转录聚合酶链反应（RT-PCR）得到了CFTR、α-、β-和γ-上皮钠通道（ENaC）以及钠钾氯协同转运蛋白1（NKCC1）的鉴定产物。CFTR抗体特异性定位于小气道管腔内衬的上皮细胞。
这些结果表明，猪的小气道具有组成性激活的Cl-电导，最有可能是由于CFTR所致。
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