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白细胞介素-5对人嗜酸性粒细胞和分化的HL-60细胞的激活作用。

Activation of human eosinophils and differentiated HL-60 cells by interleukin-5.

作者信息

Tagari P, Pecheur E I, Scheid M, Brown P, Ford-Hutchinson A W, Nicholson D

机构信息

Department of Pharmacology, Merck Frosst Centre for Therapeutic Research, Dorval, Canada.

出版信息

Int Arch Allergy Immunol. 1993;101(3):227-33. doi: 10.1159/000236450.

Abstract

The ability of recombinant human interleukin-5 (rhIL-5) to bind to human eosinophils (HEOS), and to eosinophil-like erythroleukemic cells (butyric acid differentiated HL-60 cells), and also to prime the phorbol myristate acetate ester (PMA)-induced respiratory burst of these cells was assessed. Both cell types expressed a high affinity (KD approximately 19 pM as measured ar 37 degrees C) IL-5 receptor and could be significantly primed by short (1 h) preincubation with 1 nM rhIL-5 as shown by leftward shifts of the PMA dose-response curves, and increased maximal responses (PMA EC50 without IL-5, 0.85 +/- 0.14 nM; with 1 nM IL-5, 0.47 +/- 0.15 nM, n = 6 donors; p < 0.05). In HL-60 cells, priming was dose-dependent, with an EC50 of 17 +/- 11 pM, and could be neutralised by an anti-interleukin-5 antibody (IC50 approximately 10 nM for the priming effect of 1 nM rhIL-5). A longer (24 h) incubation of HEOS with IL-5 appeared to potentiate the effect of the cytokine, which was greatest in cells from subjects with modest eosinophilia. These data suggest that interleukin-5 is a potent and rapidly acting priming agent for eosinophils, and that release of IL-5 during an allergic asthmatic reaction may contribute to the observed activation of these granulocytes.

摘要

评估了重组人白细胞介素-5(rhIL-5)与人类嗜酸性粒细胞(HEOS)、嗜酸性粒细胞样红白血病细胞(丁酸分化的HL-60细胞)结合的能力,以及引发这些细胞佛波酯肉豆蔻酸酯(PMA)诱导的呼吸爆发的能力。两种细胞类型均表达高亲和力(在37℃测量时KD约为19 pM)的IL-5受体,并且如PMA剂量反应曲线左移所示,通过与1 nM rhIL-5短时间(1小时)预孵育可被显著引发,同时最大反应增加(无IL-5时PMA的EC50为0.85±0.14 nM;有1 nM IL-5时为0.47±0.15 nM,n = 6名供体;p < 0.05)。在HL-60细胞中,引发呈剂量依赖性,EC50为17±11 pM,并且可被抗白细胞介素-5抗体中和(对于1 nM rhIL-5的引发作用,IC50约为10 nM)。HEOS与IL-5较长时间(24小时)孵育似乎可增强细胞因子的作用,在轻度嗜酸性粒细胞增多症患者的细胞中这种作用最为明显。这些数据表明白细胞介素-5是嗜酸性粒细胞的一种强效且作用迅速的引发剂,并且在过敏性哮喘反应期间IL-5的释放可能有助于观察到的这些粒细胞的激活。

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