Sakamoto Noriho, Ishimatsu Yuji, Kakugawa Tomoyuki, Yura Hirokazu, Tomonaga Masaomi, Harada Tatsuhiko, Nakashima Shota, Hara Shintaro, Hara Atsuko, Ishimoto Hiroshi, Yatera Kazuhiro, Mukae Hiroshi, Kohno Shigeru
Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
Department of Respiratory Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Respir Med. 2015 Feb;109(2):265-71. doi: 10.1016/j.rmed.2014.12.015. Epub 2015 Jan 7.
Patients with fibrosing interstitial lung diseases can develop acute exacerbation (AE). The aetiology of AE remains obscure, but neutrophils might play a pivotal role in the pathogenesis. Neutrophils store azurophil granules containing defensins that are antimicrobial peptides that also function in regulating the inflammatory response. The present study evaluates plasma levels of defensins in patients with AE of interstitial pneumonia (AE-IP) to determine their role(s) in the pathogenesis of AE-IP and whether defensins could serve as a biomarker of AE-IP.
Plasma levels of defensins including human neutrophil peptides (HNPs) and human beta defensin 2 (HBD2) were measured using ELISA in 21 patients with AE-IP, 44 with stable (S)-IP, nine with IP complicated with pulmonary infection (Infec-IP), and in 23 healthy volunteers. Lung HNP expression was immunohistochemically analyzed in biopsy and autopsy tissues diagnosed as S-IP and AE-IP.
Plasma levels of HNPs were significantly higher in patients with AE-IP than with S-IP, but did not differ from those with Infec-IP and were not associated with other clinical features and prognosis. Plasma HNP were not specific in terms of distinguishing AE-IP from S-IP. Immunohistochemical analysis showed increased HNPs expression in accumulated neutrophils from patients with AE-IP. Plasma levels of HBD2 did not differ among patients with AE-IP, S-IP and Infec-IP.
Elevated plasma levels of HNPs were higher in AE-IP than in S-IP, but not specific enough to serve as candidate biomarkers of AE-IP. Further studies are needed to clarify the role of defensins in the pathogenesis of AE-IP.
纤维化间质性肺疾病患者可发生急性加重（AE）。AE的病因仍不清楚，但中性粒细胞可能在发病机制中起关键作用。中性粒细胞储存含有防御素的嗜天青颗粒，防御素是抗菌肽，也在调节炎症反应中发挥作用。本研究评估间质性肺炎急性加重（AE-IP）患者血浆中防御素水平，以确定其在AE-IP发病机制中的作用，以及防御素是否可作为AE-IP的生物标志物。
采用酶联免疫吸附测定法（ELISA）检测21例AE-IP患者、44例稳定期（S）-IP患者、9例合并肺部感染的IP（Infec-IP）患者以及23名健康志愿者血浆中包括人中性粒细胞肽（HNPs）和人β-防御素2（HBD2）在内的防御素水平。对诊断为S-IP和AE-IP的活检和尸检组织进行免疫组织化学分析，检测肺组织中HNP的表达。
AE-IP患者血浆中HNPs水平显著高于S-IP患者，但与Infec-IP患者无差异，且与其他临床特征及预后无关。血浆HNP在区分AE-IP和S-IP方面不具有特异性。免疫组织化学分析显示，AE-IP患者积聚的中性粒细胞中HNP表达增加。AE-IP患者、S-IP患者和Infec-IP患者血浆中HBD2水平无差异。
AE-IP患者血浆中HNPs水平高于S-IP患者，但特异性不足以作为AE-IP的候选生物标志物。需要进一步研究以阐明防御素在AE-IP发病机制中的作用。
