Taooka Yasuyuki, Ohe Miki, Chen Lijun, Sutani Akihisa, Higashi Yusuke, Isobe Takeshi
Division of Medical Oncology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Shimane University, Izumo, Japan.
Respiration. 2013;86(5):367-75. doi: 10.1159/000345390. Epub 2012 Dec 19.
Repeated aspiration pneumonia is a serious problem in the elderly. In aspiration pneumonia, neutrophils play an important role in acute lung injury, while CD18-independent neutrophil transmigration pathways have also been reported in acid-aspiration pneumonia animal models. However, the involvement of IL-17A and β1 integrin still remains unclear. The β1 integrin subfamily integrin α9β1 has been shown to be expressed on human neutrophils and to mediate adhesion to extracellular matrix proteins including the vascular cell adhesion molecule-1.
To elucidate the possible involvement of β1 integrin subfamily and IL-17A in aspiration pneumonia.
We analyzed the expression levels of CD11b, CD18 and integrin α9β1 in circulating neutrophils and serum concentration of IL-17A, IL-22 and IL-23 in elderly aspiration pneumonia patients (n = 32, 14 males and 18 females, 78.8 ± 3.9 years old) at 2 time points (on the day of admission before starting antibiotics and the day after finishing antibiotics) and compared the results with those of a control group (n = 30, 13 males and 17 females, 76.1 ± 3.4 years old).
Recombinant IL-17A stimulated integrin α9β1 and CD11b expression levels in healthy human neutrophils in vitro. The expression levels of integrin α9β1 and CD11b in circulating neutrophils were significantly higher in pneumonia patients compared with the controls. In addition, serum IL-17A concentration was significantly increased in pneumonia patients. Integrin α9β1 levels positively correlated with serum IL-17A and CD18 expression levels.
These findings suggest a potential role of integrin α9β1 expressed in neutrophils and elevated serum IL-17A in extravasation of neutrophils in cases of aspiration pneumonia.
反复吸入性肺炎是老年人面临的一个严重问题。在吸入性肺炎中，中性粒细胞在急性肺损伤中起重要作用，而在酸吸入性肺炎动物模型中也报道了不依赖CD18的中性粒细胞迁移途径。然而，白细胞介素-17A（IL-17A）和β1整合素的参与情况仍不清楚。β1整合素亚家族整合素α9β1已被证明在人中性粒细胞上表达，并介导与包括血管细胞粘附分子-1在内的细胞外基质蛋白的粘附。
阐明β1整合素亚家族和IL-17A在吸入性肺炎中的可能作用。
我们分析了老年吸入性肺炎患者（n = 32，男性14例，女性18例，78.8±3.9岁）在两个时间点（开始使用抗生素前的入院当天和完成抗生素治疗后的第二天）循环中性粒细胞中CD11b、CD18和整合素α9β1的表达水平以及血清中IL-17A、IL-22和IL-23的浓度，并将结果与对照组（n = 30，男性13例，女性17例，76.1±3.4岁）进行比较。
重组IL-17A在体外刺激健康人中性粒细胞中整合素α9β1和CD11b的表达水平。与对照组相比，肺炎患者循环中性粒细胞中整合素α9β1和CD11b的表达水平显著更高。此外，肺炎患者血清IL-17A浓度显著升高。整合素α9β1水平与血清IL-17A和CD18表达水平呈正相关。
这些发现表明，中性粒细胞中表达的整合素α9β1和血清中升高的IL-17A在吸入性肺炎病例中性粒细胞外渗中可能发挥作用。
