Bicarbonate Effects on Antibacterial Immunity and Mucus Glycobiology in the Cystic Fibrosis Lung: A Review With Selected Experimental Observations.
Bicarbonate Effects on Antibacterial Immunity and Mucus Glycobiology in the Cystic Fibrosis Lung: A Review With Selected Experimental Observations.
复制标题
碳酸氢盐对囊性纤维化肺抗菌免疫和粘液糖生物学的影响：选择性实验观察的回顾。
DOI：
10.1097/im9.0000000000000101
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Nizet,Victor
中科院分区：
文献类型：
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作者：
Siew,Ruth;Ou,Tzung-Lin;Dahesh,Samira;Akong,Kathryn;Nizet,Victor
囊性纤维化（CF）的主要缺陷是CF跨膜电导调节上皮离子通道中的氯离子和碳酸氢根转运异常。呼吸道的顶端表面衬有气道表面液体（ASL）层，其由主要包含MUC 5A和MUC 5 B糖蛋白的粘蛋白组成。ASL体内平衡依赖于碳酸氢钠分泌到气道中，分泌不足会改变粘液性质，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，嗜中性粒细胞杀死铜绿假单胞菌更有效地暴露于碳酸氢钠时，和中性粒细胞的中性粒细胞胞外陷阱的形成增加碳酸氢盐浓度的存在下。生理水平的碳酸氢盐使铜绿假单胞菌对抗菌肽凯萨林菌素LL-37敏感，凯萨林菌素LL-37存在于肺ASL和中性粒细胞胞外陷阱中。碳酸氢钠在临床医学和CF患者的护理中具有各种用途，可以进一步探索作为抗假单胞菌感染的治疗辅助剂。
The primary defect in cystic fibrosis (CF) is abnormal chloride and bicarbonate transport in the CF transmembrane conductance regulator epithelial ion channel. The apical surface of the respiratory tract is lined by an airway surface liquid (ASL) layer 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 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 neutrophil extracellular traps. 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.