Muraki Masato, Kita Hirohito, Gleich Gerald J
Division of Allergic Diseases and Department of Medicine, Mayo Clinic, Rochester, MN, USA.
Department of Respiratory Medicine and Allergology, Kindai University Nara Hospital, 1248-1 Otoda-cho, Ikoma, Nara, 630-0293, Japan.
Clin Mol Allergy. 2020 Dec 2;18(1):24. doi: 10.1186/s12948-020-00138-1.
Eosinophils play an important role in allergic inflammation. Glucocorticosteroids have been used as an anti-inflammatory medication for inflammatory diseases involving eosinophil infiltration. Some effect of nebulized lidocaine has been reported when treating certain patients with asthma, which is also an inflammatory disease. The goal of this study was to examine the effects of dexamethasone and lidocaine on eosinophil proliferation and differentiation using a model of human umbilical cord blood mononuclear cells (UCMC) cultured with IL-5.
UCMC were cultured with IL-5 (5 ng/mL) for 4 weeks. The effects of dexamethasone and lidocaine on the number and morphology of eosinophilic cells were visualized with Wright-Giemsa and cyanide-resistant peroxidase stains. Moreover, the effect on eosinophil-derived neurotoxin (EDN) and eosinophil peroxidase (EPX) contents in cultured cells were evaluated using radioimmunoassay.
The number of eosinophilic cells and EDN and EPX content in cultured cells increased in a time-dependent manner in the presence of IL-5. Dexamethasone treatment slightly decreased the number of eosinophilic cells in one week, but this effect was lost in 2-4 weeks. Macrophages in cultured UCMC treated with dexamethasone contained more eosinophil granule proteins. Both EDN and EPX content in cultured cells were reduced by dexamethasone. Lidocaine decreased the number of eosinophilic cells and reduced both EDN and EPX contents in cultured cells.
Dexamethasone suppressed the production of eosinophil granule proteins and may also induce apoptosis of eosinophils, while lidocaine suppresses eosinophilopoiesis.
嗜酸性粒细胞在过敏性炎症中起重要作用。糖皮质激素已被用作治疗涉及嗜酸性粒细胞浸润的炎症性疾病的抗炎药物。在治疗某些哮喘患者(哮喘也是一种炎症性疾病)时,已报道雾化利多卡因有一定效果。本研究的目的是使用白细胞介素-5(IL-5)培养的人脐带血单个核细胞(UCMC)模型,研究地塞米松和利多卡因对嗜酸性粒细胞增殖和分化的影响。
将UCMC与IL-5(5 ng/mL)培养4周。用地衣红和抗氰过氧化物酶染色观察地塞米松和利多卡因对嗜酸性细胞数量和形态的影响。此外,采用放射免疫分析法评估对培养细胞中嗜酸性粒细胞衍生神经毒素(EDN)和嗜酸性粒细胞过氧化物酶(EPX)含量的影响。
在IL-5存在的情况下,培养细胞中嗜酸性细胞的数量以及EDN和EPX含量呈时间依赖性增加。地塞米松治疗在1周时使嗜酸性细胞数量略有减少,但在2 - 4周时这种效果消失。用地塞米松处理的培养UCMC中的巨噬细胞含有更多嗜酸性粒细胞颗粒蛋白。地塞米松降低了培养细胞中EDN和EPX的含量。利多卡因减少了培养细胞中嗜酸性细胞的数量,并降低了EDN和EPX的含量。
地塞米松抑制嗜酸性粒细胞颗粒蛋白的产生,也可能诱导嗜酸性粒细胞凋亡,而利多卡因抑制嗜酸性粒细胞生成。