Patel Shruti, Nugent Kenneth
Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
J Thorac Dis. 2023 Oct 31;15(10):5773-5783. doi: 10.21037/jtd-23-846. Epub 2023 Sep 22.
Cystic fibrosis (CF) is a disorder that affects the cystic fibrosis transmembrane conductance regulator (CFTR). Without properly functioning CFTR channels, chloride does not exit respiratory epithelial cells, and consequently the mucus lining the surface of the cells becomes thick. This viscous mucus accumulates and causes abnormal function of the mucociliary apparatus, which can lead to bacterial colonization, infections with () and (), and eventually lung damage. Recent studies have shown that the increased susceptibility to respiratory infections in CF patients may also be due to defects in neutrophil function, but the exact mechanism is uncertain.
The PubMed database was searched on February 10, 2023 and again on July 23, 2023 to compile a comprehensive list of clinical and experimental studies to evaluate neutrophil function in CF. The first search included a combination of MeSH terms: "cystic fibrosis" and "neutrophils/physiology". A separate second search included a combination of the MeSH terms: "neutrophils" and "cystic fibrosis transmembrane conductance regulator".
Neutrophils from patients with CF have decreased transfer of chloride into phagolysosomes after bacterial ingestion and have dysregulated degranulation. This reduces the production of toxic oxidative radicals, especially hypochlorous acid (HOCl), and reduces bactericidal activity. CFTR potentiators correct the dysregulated degranulation in patients with CF and increased neutrophil killing activity. A reduced concentration of chloride in assays also reduces neutrophil killing activity; these observations are relevant to the reduced chloride concentrations in respiratory secretions in patients with CF.
This literature review summarizes studies that demonstrate that an important defect in CF neutrophils lies in the oxygen-dependent pathway in phagolysosomes and studies with ivacaftor demonstrate that this drug corrects CF neutrophil function. These studies demonstrate the potential utility of using easily available neutrophils to study drug effects in CF patients.
囊性纤维化（CF）是一种影响囊性纤维化跨膜传导调节因子（CFTR）的疾病。由于CFTR通道功能不正常，氯离子无法从呼吸道上皮细胞排出，因此细胞表面的黏液会变稠。这种黏稠的黏液会积聚并导致黏液纤毛装置功能异常，进而引发细菌定植、感染（如铜绿假单胞菌和金黄色葡萄球菌），最终导致肺损伤。最近的研究表明，CF患者对呼吸道感染易感性增加也可能是由于中性粒细胞功能缺陷，但确切机制尚不清楚。
于2023年2月10日和2023年7月23日在PubMed数据库进行检索，以汇编评估CF患者中性粒细胞功能的临床和实验研究的综合列表。第一次检索包括以下医学主题词的组合：“囊性纤维化”和“中性粒细胞/生理学”。第二次单独检索包括以下医学主题词的组合：“中性粒细胞”和“囊性纤维化跨膜传导调节因子”。
CF患者的中性粒细胞在吞噬细菌后，氯离子向吞噬溶酶体的转运减少，脱颗粒失调。这会减少有毒氧化自由基的产生，尤其是次氯酸（HOCl），并降低杀菌活性。CFTR增强剂可纠正CF患者的脱颗粒失调，并增强中性粒细胞杀伤活性。体外实验中较低的氯离子浓度也会降低中性粒细胞杀伤活性；这些观察结果与CF患者呼吸道分泌物中氯离子浓度降低有关。
本综述总结了多项研究，这些研究表明CF中性粒细胞的一个重要缺陷在于吞噬溶酶体中的氧依赖途径，并且使用依伐卡托的研究表明该药物可纠正CF中性粒细胞功能。这些研究证明了利用易于获取的中性粒细胞来研究CF患者药物疗效的潜在效用。
