Disruptive effects of anion secretion inhibitors on airway mucus morphology in isolated perfused pig lung.
Disruptive effects of anion secretion inhibitors on airway mucus morphology in isolated perfused pig lung.
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阴离子分泌抑制剂对离体灌注猪肺气道粘液形态的破坏性影响。
DOI：
10.1113/jphysiol.2002.035923
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Ballard,StephenT
中科院分区：
文献类型：
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作者：
Trout,Laura;Townsley,MaryI;Bowden,AmyL;Ballard,StephenT
由于阴离子分泌抑制剂重现囊性纤维化（CF）肺疾病的重要方面，这些拮抗剂对气道粘液形态的影响进行了评估，在离体灌注猪肺。布美他尼和二甲阿米洛利的最大抑制浓度分别阻断猪气道中的Cl−和HCO3−分泌，诱导气道表面形成致密的“膏状”粘液，消耗纤毛周液和纤毛塌陷。当肺也暴露于氨甲酰甲胆碱以刺激粘膜下腺体分泌时，当膏状粘液覆盖> 98%的气道表面时，这种作用更加明显。氨甲酰甲胆碱也减少腺导管粘蛋白含量的情况下，但不存在，阴离子分泌抑制剂。阴离子分泌抑制剂不会诱导杯状细胞脱颗粒的可测量的增加。我们的结论是，抑制阴离子和液体分泌在猪肺破坏气道表面粘液的正常形态，提供进一步的证据表明，阴离子分泌受损单独可以解释CF肺病的关键方面。
Since anion secretion inhibitors reproduce important aspects of cystic fibrosis (CF) lung disease, the effects of these antagonists on airway mucus morphology were assessed in isolated perfused pig lungs. Maximal inhibitory concentrations of bumetanide and dimethylamiloride, which respectively block Cl−and HCO3−secretion in porcine airways, induced the formation of dense ‘plastered’ mucus on the airway surface, depletion of periciliary fluid and collapse of cilia. This effect was more pronounced when lungs were also exposed to bethanechol to stimulate submucosal gland secretion, when plastered mucus covered > 98% of the airway surface. Bethanechol also reduced gland duct mucin content in the absence, but not presence, of the anion secretion inhibitors. Anion secretion inhibitors did not induce measurable increases in goblet cell degranulation. We conclude that inhibition of anion and liquid secretion in porcine lungs disrupts the normal morphology of airway surface mucus, providing further evidence that impaired anion secretion alone could account for critical aspects of CF lung disease.