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 a...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.展开更多
基金supported by NIH training fellowships 5T32HD08798 and 5K12HL141956 to RS and NIH research grant R01AI145310 to VN.
文摘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.
