Laboratory of Pulmonology, Department of Pulmonology, Lithuanian University of Health Sciences, LT-44307 Kaunas, Lithuania.
Department of Pulmonology, Lithuanian University of Health Sciences, LT-44307 Kaunas, Lithuania.
Cells. 2020 May 18;9(5):1248. doi: 10.3390/cells9051248.
Eosinophils subtypes as lung-resident (rEOS) and inflammatory (iEOS) eosinophils are different in surface protein expression, functions, response to IL-5 and localization in lungs. rEOS- and iEOS-like eosinophils are found in blood; thus, we aimed to investigate their quantity and survivability in asthma patients. A total of 40 individuals were included: 10 steroid-free non-severe allergic asthma (AA), and 18 severe non-allergic eosinophilic asthma (SNEA) patients, the control group consisted of 12 healthy non-smoking subjects (HS). A bronchial challenge with allergen was performed for AA patients and HS. Blood eosinophils subtyping was completed with magnetic beads' conjugated antibodies against surface CD62L. Eosinophils adhesion to hTERT airway smooth muscle (ASM) cells was measured by evaluating their peroxidase activity and viability by annexin V and propidium iodide staining. We found that the predominant blood eosinophil subtype in AA patients was iEOS, while rEOS prevailed in SNEA patients (p < 0.05). Moreover, rEOS demonstrated higher adhesion intensity compared with iEOS in all investigated groups. Both eosinophils subtypes of SNEA patients had higher survivability over the AA group. However, iEOS survivability from AA and SNEA groups was higher compared with rEOS under standard conditions, when rEOS survivability increased after their incubation with ASM cells. Bronchial allergen challenge abolished the dominance of blood iEOS in AA patients and prolonged only iEOS survivability. Though the challenge did not affect the adhesion of any eosinophils subtypes, the direct dependence of rEOS and iEOS survivability on their interaction with ASM cells was revealed (p < 0.05). These findings provide the premise for eosinophils subtype-oriented asthma treatment.
嗜酸性粒细胞亚群分为肺驻留(rEOS)和炎症(iEOS)嗜酸性粒细胞,它们在表面蛋白表达、功能、对 IL-5 的反应和在肺部的定位上有所不同。rEOS 和 iEOS 样嗜酸性粒细胞存在于血液中;因此,我们旨在研究它们在哮喘患者中的数量和存活率。共纳入 40 名个体:10 名无类固醇的非严重过敏哮喘(AA)患者和 18 名严重非过敏嗜酸性粒细胞性哮喘(SNEA)患者,对照组由 12 名健康不吸烟的受试者(HS)组成。对 AA 患者和 HS 进行了过敏原支气管激发试验。使用表面 CD62L 抗体偶联的磁性珠对血液嗜酸性粒细胞进行亚群分型。通过评估过氧化物酶活性和 annexin V 和碘化丙啶染色的细胞活力来测量嗜酸性粒细胞与 hTERT 气道平滑肌(ASM)细胞的黏附。我们发现,AA 患者血液中主要的嗜酸性粒细胞亚群是 iEOS,而 SNEA 患者则以 rEOS 为主(p<0.05)。此外,在所有研究组中,rEOS 与 iEOS 相比,其黏附强度更高。SNEA 患者的两种嗜酸性粒细胞亚群的存活率均高于 AA 组。然而,在标准条件下,与 rEOS 相比,AA 和 SNEA 组的 iEOS 存活率更高,而 rEOS 在与 ASM 细胞孵育后存活率增加。支气管过敏原激发试验消除了 AA 患者血液中 iEOS 的优势,并仅延长了 iEOS 的存活率。虽然该试验不影响任何嗜酸性粒细胞亚群的黏附,但揭示了 rEOS 和 iEOS 存活率与其与 ASM 细胞相互作用的直接依赖性(p<0.05)。这些发现为基于嗜酸性粒细胞亚群的哮喘治疗提供了前提。