Siew Ruth, Ou Tzung-Lin, Dahesh Samira, Akong Kathryn, Nizet Victor
Department of Pediatrics, University of California San Diego, La Jolla, California, USA.
School of Medicine, China Medical University, Taichung, Taiwan.
Infect Microbes Dis. 2022 Sep;4(3):103-110. doi: 10.1097/im9.0000000000000101. Epub 2022 Aug 16.
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 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 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 infections.
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）上皮离子通道中氯离子和碳酸氢根离子转运异常。呼吸道的顶端表面覆盖着一层气道表面液体层（ASL），该液体层由主要包含MUC5A和MUC5B糖蛋白的粘蛋白组成。ASL的内环境稳定取决于碳酸氢钠向气道的分泌，分泌不足会改变黏液特性，导致气道阻塞、炎症和感染。肺部离子转运异常的下游效应包括固有免疫防御改变。我们观察到，中性粒细胞在接触碳酸氢钠后杀菌效率更高，并且在碳酸氢盐浓度增加的情况下，中性粒细胞形成中性粒细胞胞外陷阱（NETs）的能力增强。生理水平的碳酸氢盐可增强对抗微生物肽cathelicidin LL-37的敏感性，该抗菌肽存在于肺部ASL和NETs中。碳酸氢钠在临床医学和CF患者护理中有多种用途，可作为抗感染治疗辅助手段作进一步探索。
