Ueda Yutaka, Nakagome Kazuyuki, Kobayashi Takehito, Noguchi Toru, Soma Tomoyuki, Ohashi-Doi Katsuyo, Tokuyama Kenichi, Nagata Makoto
Department of Respiratory Medicine, Saitama Medical University, Saitama, Japan.
Department of Pediatrics, Saitama Medical University, Saitama, Japan.
Asia Pac Allergy. 2020 Apr 22;10(2):e15. doi: 10.5415/apallergy.2020.10.e15. eCollection 2020 Apr.
Even in subjects who are not sensitized to house dust mite (HDM), allergic symptoms can be clinically aggravated by exposure to dust. We previously reported that (), an important HDM, or Der f 1, a major allergen of , induced the effector functions of eosinophils, which may be an important mechanism for HDM-induced symptoms in nonsensitized patients. In a clinical setting, β2-adrenergic agonists, such as salbutamol and formoterol, are used for the treatment of asthma attacks or exacerbation to release the airway obstruction. Several reports have suggested that some β2-adrenergic agonists have an anti-inflammatory capacity.
In this study, we investigated whether β2-adrenergic agonist could modify the - or Der f 1-induced activation of eosinophils.
Blood eosinophils obtained from healthy donors were preincubated with either formoterol (1 μM), salbutamol (1 μM), or buffer control and then stimulated with extract (1 μg/mL) or Der f 1 (100 pg/mL). Eosinophil adhesion to intercellular adhesion molecule (ICAM)-1 was measured using eosinophil peroxidase assays. Generation of superoxide anion (O ) was examined based on the superoxide dismutase-inhibitable reduction of cytochrome C. Eosinophil-derived neurotoxin (EDN) concentrations in cell media were measured by enzyme-linked immunosorbent assay.
Formoterol, but not salbutamol, suppressed the - or Der f 1-induced eosinophil adhesion to ICAM-1. Furthermore, formoterol, but not salbutamol, suppressed -induced O generation or EDN release. Neither formoterol nor salbutamol suppressed spontaneous eosinophil adhesion, O generation, or EDN release.
These findings suggested that formoterol, but not salbutamol, suppressed - or Der f 1-induced eosinophil activation when used at the same concentration. Therefore, formoterol could potentially be used for the treatment of bronchial asthma via both bronchodilation and anti-inflammatory effect.
即使在对屋尘螨（HDM）不敏感的个体中，接触灰尘也可使过敏症状在临床上加重。我们之前报道过，一种重要的HDM，即Der f 1（ 的主要变应原）可诱导嗜酸性粒细胞的效应功能，这可能是HDM诱导非敏感患者出现症状的重要机制。在临床环境中，β2 - 肾上腺素能激动剂，如沙丁胺醇和福莫特罗，用于治疗哮喘发作或病情加重以缓解气道阻塞。一些报道表明某些β2 - 肾上腺素能激动剂具有抗炎能力。
在本研究中，我们调查了β2 - 肾上腺素能激动剂是否能改变 或Der f 1诱导的嗜酸性粒细胞活化。
从健康供体获取的血液嗜酸性粒细胞先用福莫特罗（1 μM）、沙丁胺醇（1 μM）或缓冲液对照进行预孵育，然后用 提取物（1 μg/mL）或Der f 1（100 pg/mL）刺激。使用嗜酸性粒细胞过氧化物酶测定法测量嗜酸性粒细胞与细胞间黏附分子（ICAM）-1的黏附。基于超氧化物歧化酶抑制的细胞色素C还原来检测超氧阴离子（O ）的生成。通过酶联免疫吸附测定法测量细胞培养基中嗜酸性粒细胞衍生神经毒素（EDN）的浓度。
福莫特罗而非沙丁胺醇抑制了 或Der f 1诱导的嗜酸性粒细胞与ICAM - 1的黏附。此外，福莫特罗而非沙丁胺醇抑制了 诱导的O 生成或EDN释放。福莫特罗和沙丁胺醇均未抑制自发的嗜酸性粒细胞黏附、O 生成或EDN释放。
这些发现表明，在相同浓度下使用时，福莫特罗而非沙丁胺醇抑制了 或Der f 1诱导的嗜酸性粒细胞活化。因此，福莫特罗可能通过支气管扩张和抗炎作用潜在地用于治疗支气管哮喘。
