Durham S R, Ying S, Varney V A, Jacobson M R, Sudderick R M, Mackay I S, Kay A B, Hamid Q A
Department of Allergy and Clinical Immunology, National Heart & Lung Institute, London, England, U.K.
J Immunol. 1992 Apr 15;148(8):2390-4.
Tissue eosinophilia is characteristic of human atopic allergic inflammation, although the mechanism is largely unknown. In this study we test the hypothesis that eosinophil infiltration during allergen-provoked rhinitis in hayfever sufferers may occur as a consequence of activation of a population of cells having a characteristic cytokine profile equivalent to the murine Th lymphocyte Th2 subset. Biopsies of the nasal inferior turbinate were obtained from 10 grass pollen-sensitive patients 24 h after local nasal provocation with allergen and after a control challenge with the allergen diluent. Biopsies were divided into two and subsequently processed for in situ hybridization using 35S-labeled RNA probes for selected cytokines and for immunohistology using an eosinophil granule mAb (EG2) which recognizes secreting eosinophils. At allergen-challenged sites compared with control sites there were significant increases in mRNA+ cells for IL-3 (p less than 0.04), IL-4 (p = 0.01), IL-5 (p = 0.02) and granulocyte/macrophage-CSF (p = 0.03). In contrast, only occasional hybridization signals were observed for IL-2 and IFN-gamma at both allergen and control sites. After allergen there was an increase (p = 0.01) in EG2+ eosinophils and significant correlations were observed between EG2+ cells and mRNA expression for "Th2-type" cytokines, particularly IL-5 (r = 0.90, p less than 0.0001). These results demonstrate that recruitment of eosinophils during human allergen-induced rhinitis is associated with cells expressing mRNA for IL-3, IL-4, IL-5, and granulocyte/macrophage-CSF.
组织嗜酸性粒细胞增多是人类特应性过敏性炎症的特征,尽管其机制大多未知。在本研究中,我们检验了这样一个假设:花粉症患者在变应原诱发的鼻炎期间嗜酸性粒细胞浸润,可能是由于一群具有与小鼠Th淋巴细胞Th2亚群相当的特征性细胞因子谱的细胞被激活所致。在对10名对草花粉敏感的患者进行局部鼻内变应原激发后24小时以及用变应原稀释剂进行对照激发后,获取下鼻甲活检组织。将活检组织分成两份,随后分别用于使用针对选定细胞因子的35S标记RNA探针进行原位杂交,以及使用识别分泌型嗜酸性粒细胞的嗜酸性粒细胞颗粒单克隆抗体(EG2)进行免疫组织学检查。与对照部位相比,在变应原激发部位,IL-3(p<0.04)、IL-4(p = 0.01)、IL-5(p = 0.02)和粒细胞/巨噬细胞集落刺激因子(p = 0.03)的mRNA+细胞显著增加。相比之下,在变应原和对照部位,仅偶尔观察到IL-2和IFN-γ的杂交信号。变应原激发后,EG2+嗜酸性粒细胞增加(p = 0.01),并且在EG2+细胞与“Th2型”细胞因子的mRNA表达之间观察到显著相关性,尤其是IL-5(r = 0.90,p<0.0001)。这些结果表明,人类变应原诱导的鼻炎期间嗜酸性粒细胞的募集与表达IL-3、IL-4、IL-5和粒细胞/巨噬细胞集落刺激因子mRNA的细胞有关。