Schmid-Grendelmeier Peter, Altznauer Frank, Fischer Barbra, Bizer Christian, Straumann Alex, Menz Günter, Blaser Kurt, Wüthrich Brunello, Simon Hans-Uwe
Swiss Institute for Allergy and Asthma Research, Davos-Platz, Switzerland.
J Immunol. 2002 Jul 15;169(2):1021-7. doi: 10.4049/jimmunol.169.2.1021.
IL-13 is an immunoregulatory and effector cytokine in allergic diseases such as bronchial asthma. A variety of immune and non-immune cells are known as IL-13 producers. In this study we investigated whether and under what conditions human eosinophils generate IL-13. Freshly isolated highly purified peripheral blood eosinophils from patients with several eosinophilic inflammatory diseases and from normal control individuals were investigated. We observed that blood eosinophils from patients suffering from bronchial asthma, atopic dermatitis, parasitic infections, hypereosinophilic syndrome, and idiopathic eosinophilic esophagitis expressed IL-13, as assessed by ELISA, ELISPOT assay, flow cytometry, and immunocytochemistry. By using nasal polyp tissues and immunohistochemistry, we demonstrated IL-13 expression in eosinophils under in vivo conditions. In contrast, blood eosinophils from control individuals as well as blood neutrophils from both eosinophilic and control patients did not produce detectable IL-13 levels. However, when blood eosinophils from control individuals were stimulated with GM-CSF or IL-5 in vitro, they generated IL-13 mRNA and protein, suggesting that IL-13 expression by eosinophils under inflammatory conditions is a cytokine-driven process. Stimulation of blood eosinophils containing IL-13 by eotaxin resulted in a rapid release of this cytokine. Eosinophil-derived IL-13 was functional, as it increased the surface expression of the low affinity IgE receptor (CD23) on purified B cells. In conclusion, human eosinophils are able to produce and release functional IL-13 in eosinophilic inflammatory responses.
白细胞介素-13是支气管哮喘等过敏性疾病中的一种免疫调节和效应细胞因子。多种免疫细胞和非免疫细胞被认为是白细胞介素-13的产生细胞。在本研究中，我们调查了人类嗜酸性粒细胞是否以及在何种条件下产生白细胞介素-13。我们研究了从患有几种嗜酸性粒细胞炎症性疾病的患者和正常对照个体中新鲜分离的高度纯化的外周血嗜酸性粒细胞。通过酶联免疫吸附测定（ELISA）、酶联免疫斑点测定（ELISPOT）、流式细胞术和免疫细胞化学评估，我们观察到患有支气管哮喘、特应性皮炎、寄生虫感染、高嗜酸性粒细胞综合征和特发性嗜酸性粒细胞食管炎的患者的血液嗜酸性粒细胞表达白细胞介素-13。通过使用鼻息肉组织和免疫组织化学，我们证实在体内条件下嗜酸性粒细胞中有白细胞介素-13表达。相比之下，对照个体的血液嗜酸性粒细胞以及嗜酸性粒细胞患者和对照患者的血液中性粒细胞均未产生可检测到的白细胞介素-13水平。然而，当对照个体的血液嗜酸性粒细胞在体外受到粒细胞-巨噬细胞集落刺激因子（GM-CSF）或白细胞介素-5刺激时，它们产生白细胞介素-13信使核糖核酸（mRNA）和蛋白质，这表明炎症条件下嗜酸性粒细胞的白细胞介素-13表达是一个细胞因子驱动的过程。嗜酸性粒细胞趋化因子刺激含有白细胞介素-13的血液嗜酸性粒细胞导致该细胞因子迅速释放。嗜酸性粒细胞衍生的白细胞介素-13具有功能，因为它增加了纯化B细胞上低亲和力免疫球蛋白E受体（CD23）的表面表达。总之，人类嗜酸性粒细胞能够在嗜酸性粒细胞炎症反应中产生并释放具有功能的白细胞介素-13。
