Department of Internal Medicine, University of Iowa, Iowa City, 52242, USA.
Cell. 2010 Dec 10;143(6):911-23. doi: 10.1016/j.cell.2010.11.029.
Defective transepithelial electrolyte transport is thought to initiate cystic fibrosis (CF) lung disease. Yet, how loss of CFTR affects electrolyte transport remains uncertain. CFTR⁻(/)⁻ pigs spontaneously develop lung disease resembling human CF. At birth, their airways exhibit a bacterial host defense defect, but are not inflamed. Therefore, we studied ion transport in newborn nasal and tracheal/bronchial epithelia in tissues, cultures, and in vivo. CFTR⁻(/)⁻ epithelia showed markedly reduced Cl⁻ and HCO₃⁻ transport. However, in contrast to a widely held view, lack of CFTR did not increase transepithelial Na(+) or liquid absorption or reduce periciliary liquid depth. Like human CF, CFTR⁻(/)⁻ pigs showed increased amiloride-sensitive voltage and current, but lack of apical Cl⁻ conductance caused the change, not increased Na(+) transport. These results indicate that CFTR provides the predominant transcellular pathway for Cl⁻ and HCO₃⁻ in porcine airway epithelia, and reduced anion permeability may initiate CF airway disease.
跨上皮电解质转运缺陷被认为是引发囊性纤维化（CF）肺部疾病的原因。然而，CFTR 的缺失如何影响电解质转运仍不确定。CFTR⁻（/-）⁻猪会自发地患上类似于人类 CF 的肺部疾病。在出生时，它们的气道表现出细菌宿主防御缺陷，但没有炎症。因此，我们在组织、培养物和体内研究了新生鼻和气管/支气管上皮中的离子转运。CFTR⁻（/-）⁻上皮的 Cl⁻和 HCO₃⁻转运明显减少。然而，与普遍观点相反，CFTR 的缺乏并没有增加跨上皮 Na⁺或液体吸收，也没有减少纤毛周围液体的深度。与人类 CF 一样，CFTR⁻（/-）⁻猪表现出增加的阿米洛利敏感电压和电流，但缺乏顶端 Cl⁻电导导致了这种变化，而不是增加的 Na⁺转运。这些结果表明，CFTR 是猪气道上皮中 Cl⁻和 HCO₃⁻的主要细胞间途径，阴离子通透性降低可能引发 CF 气道疾病。
