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美泊利珠单抗用于成人重度嗜酸性粒细胞性哮喘的管理:当前证据与实践经验

Mepolizumab in the management of severe eosinophilic asthma in adults: current evidence and practical experience.

作者信息

Varricchi Gilda, Bagnasco Diego, Ferrando Matteo, Puggioni Francesca, Passalacqua Giovanni, Canonica Giorgio W

机构信息

Department of Translational Medical Sciences, Division of Clinical Immunology and Allergy, University of Naples Federico II, Naples, Italy.

Allergy & Respiratory Diseases Clinic-DIMI-University of Genova, Italy.

出版信息

Ther Adv Respir Dis. 2017 Jan;11(1):40-45. doi: 10.1177/1753465816673303. Epub 2016 Nov 17.

Abstract

Eosinophils represent approximately 1% of peripheral blood leukocytes in normal donors and their maturation and differentiation in the bone marrow are mainly regulated by interleukin (IL)-5 [Broughton et al. 2015]. IL-5, a cytokine that belongs to the β common-chain family, together with IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF), stimulates also the activation and survival of eosinophils and, to some extent, of basophils. IL-5 binds to a heterodimer receptor composed of the specific subunit IL-5Rα and a common subunit βc shared with IL-3 and GM-CSF. Human eosinophils express approximately a three-fold higher level of IL-5Rα compared with basophils. Major sources of IL-5 are T-helper 2 (Th2) cells, mast cells, CD34+ progenitor cells, invariant natural killer (NK) T-cells, group 2 innate lymphoid cells (ILC2s), and eosinophils themselves. ILC2s control not only eosinophil number but also their circadian cycling through the production of IL-5.

摘要

在正常供体中,嗜酸性粒细胞约占外周血白细胞的1%,它们在骨髓中的成熟和分化主要受白细胞介素(IL)-5调控[布劳顿等人,2015年]。IL-5是一种属于β共同链家族的细胞因子,与IL-3和粒细胞-巨噬细胞集落刺激因子(GM-CSF)一起,还能刺激嗜酸性粒细胞以及在一定程度上刺激嗜碱性粒细胞的活化和存活。IL-5与由特异性亚基IL-5Rα和与IL-3及GM-CSF共享的共同亚基βc组成的异二聚体受体结合。与嗜碱性粒细胞相比,人类嗜酸性粒细胞表达的IL-5Rα水平约高两倍。IL-5的主要来源是辅助性T细胞2(Th2)、肥大细胞、CD34+祖细胞、不变自然杀伤(NK)T细胞、2型固有淋巴细胞(ILC2)以及嗜酸性粒细胞自身。ILC2不仅控制嗜酸性粒细胞数量,还通过产生IL-5控制其昼夜循环。

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