PDF(Pubmed)
Abstract：
The primary defect in cystic fibrosis (CF) is abnormal chloride and bicarbonate transport in the cystic fibrosis transmembrane conductance regulator (CFTR) epithelial ion channel. The apical surface of the respiratory tract is lined by an airway surface liquid layer (ASL) composed of mucin comprising mainly MUC5A and MUC5B glycoproteins. ASL homeostasis depends on sodium bicarbonate secretion into the airways and secretion deficits alter mucus properties leading to airway obstruction, inflammation, and infections. Downstream effects of abnormal ion transport in the lungs include altered intrinsic immune defenses. We observed that neutrophils killed Pseudomonas aeruginosa more efficiently when it had been exposed to sodium bicarbonate, and formation of neutrophil extracellular traps (NETs) by neutrophils was augmented in the presence of increasing bicarbonate concentrations. Physiological levels of bicarbonate sensitized P. aeruginosa to the antimicrobial peptide cathelicidin LL-37, which is present in both lung ASL and in NETs. Sodium bicarbonate has various uses in clinical medicine and in the care of CF patients, and could be further explored as a therapeutic adjunct against Pseudomonas infections.
摘要：
囊性纤维化（CF）的主要缺陷是囊性纤维化跨膜传导调节因子（CFTR）上皮离子通道中的氯化物和碳酸氢盐转运异常。呼吸道的顶表面由由主要包含MUC5A和MUC5B糖蛋白的粘蛋白组成的气道表面液体层(ASL)衬里。ASL稳态取决于碳酸氢钠分泌到气道和分泌缺陷改变粘液特性导致气道阻塞。炎症,和感染。肺中异常离子转运的下游效应包括改变的内在免疫防御。我们观察到中性粒细胞在暴露于碳酸氢钠时更有效地杀死铜绿假单胞菌，在碳酸氢盐浓度增加的情况下，嗜中性粒细胞形成的嗜中性粒细胞胞外陷阱（NETs）增加。碳酸氢盐使铜绿假单胞菌对存在于肺ASL和NET中的抗微生物肽cathelicidinLL-37的生理水平敏感。碳酸氢钠在临床医学和CF患者的护理中具有多种用途，并且可以进一步探索作为针对假单胞菌感染的治疗辅助手段。
