Emory+Children's Center for Cystic Fibrosis Research, Division of Pulmonology, Allergy/Immunology, Cystic Fibrosis and Sleep, Emory University School of Medicine, Atlanta, GA 30322, USA.
J Investig Med. 2013 Aug;61(6):1018-25. doi: 10.2310/JIM.0b013e31829cbd14.
Patients with cystic fibrosis (CF) develop chronic bacterial infections in the respiratory tract, reflecting dysfunctional innate immunity. Neutrophil gelatinase-associated lipocalin (NGAL) has 2 functions: one as an antibacterial host defense protein and the other as a physiological iron carrier. Neutrophil gelatinase-associated lipocalin (NGAL) has been validated as a biomarker for early kidney disease. The aim of this study was to determine whether NGAL could serve as a marker of acute pulmonary exacerbations in CF by measuring NGAL levels in serum samples from subjects with CF during stable clinic visits and during hospitalization for pulmonary exacerbations and comparing these levels to healthy controls and to patients without CF with significant infection. In addition, we aimed to determine if innate immunity cells other than neutrophils act as a source of NGAL.
Circulating NGAL levels were measured by enzyme-linked immunosorbent assay in serum samples from 30 subjects with CF when hospitalized for an acute pulmonary exacerbation, 33 subjects with CF during stable clinic visits, 33 patients with sepsis, and 21 healthy controls. Secreted NGAL from CF and healthy control peripheral monocytes infected with Pseudomonas aeruginosa was also measured by enzyme-linked immunosorbent assay.
Serum NGAL levels were elevated in the patients with CF compared to the healthy controls (P < 0.001). However, no difference in serum NGAL levels was found between subjects with CF with stable disease compared to subjects with CF undergoing pulmonary exacerbation. Furthermore, peripheral monocytes from CF and subjects without CF secreted NGAL upon infection with Pseudomonas aeruginosa and thereby may be contributing to the circulating NGAL levels observed.
Our data show that peripheral monocytes secrete NGAL, and serum NGAL levels are widely distributed among subjects with CF, being elevated both when clinically stable and during a pulmonary exacerbation and thus NGAL is not a sensitive biomarker for pulmonary exacerbations.
囊性纤维化（CF）患者在呼吸道中会发展出慢性细菌感染，这反映了先天免疫功能障碍。中性粒细胞明胶酶相关脂质运载蛋白（NGAL）具有 2 种功能：一种是作为抗菌宿主防御蛋白，另一种是作为生理铁载体。中性粒细胞明胶酶相关脂质运载蛋白（NGAL）已被验证为早期肾病的生物标志物。本研究旨在通过测量 CF 患者在稳定就诊期间和因肺部感染加重而住院期间的血清样本中的 NGAL 水平，确定 NGAL 是否可以作为 CF 急性肺部加重的标志物，并将这些水平与健康对照者和无 CF 但有严重感染的患者进行比较。此外，我们旨在确定除中性粒细胞以外的先天免疫细胞是否作为 NGAL 的来源。
通过酶联免疫吸附试验测量 30 例 CF 患者因急性肺部加重住院、33 例 CF 患者稳定就诊、33 例脓毒症患者和 21 例健康对照者的血清 NGAL 水平。还通过酶联免疫吸附试验测量 CF 和健康对照者外周单核细胞感染铜绿假单胞菌后分泌的 NGAL。
与健康对照者相比，CF 患者的血清 NGAL 水平升高（P<0.001）。然而，在稳定疾病的 CF 患者与发生肺部加重的 CF 患者之间，血清 NGAL 水平无差异。此外，CF 和非 CF 患者的外周单核细胞在感染铜绿假单胞菌后分泌 NGAL，这可能导致观察到的循环 NGAL 水平升高。
我们的数据表明，外周单核细胞分泌 NGAL，并且 CF 患者的血清 NGAL 水平广泛分布，在临床稳定和肺部加重时均升高，因此 NGAL 不是肺部加重的敏感生物标志物。
