Minshall E M, Cameron L, Lavigne F, Leung D Y, Hamilos D, Garcia-Zepada E A, Rothenberg M, Luster A D, Hamid Q
Meakins-Christie Laboratories, McGill University, Notre Dame Hospital, Montreal, Quebec, Canada.
Am J Respir Cell Mol Biol. 1997 Dec;17(6):683-90. doi: 10.1165/ajrcmb.17.6.2865.
Eotaxin is an eosinophil-specific chemokine associated with the recruitment of eosinophils to the site of allergic inflammation. The aims of this study were to determine the expression of eotaxin in nasal biopsies from allergic and nonallergic individuals with chronic severe sinusitis, and to examine whether the expression of this chemokine is upregulated following allergen challenge in the nasal mucosa of patients with allergic rhinitis. We also undertook to phenotype of inflammatory cells within the submucosa expressing eotaxin mRNA. Nasal turbinate tissue from 16 individuals with allergic or nonallergic chronic sinusitis and 10 normal controls were examined for the presence of eotaxin mRNA and immunoreactivity by in situ hybridization and immunocytochemistry. The numbers of cells expressing eotaxin mRNA were also determined after either allergen or diluent challenge in atopic subjects with a history of allergic rhinitis. There was a constitutive expression of eotaxin-immunoreactivity and the presence of eotaxin mRNA-positive cells in nasal biopsies from normal individuals. Compared with normal controls, the numbers of cells expressing eotaxin mRNA and protein were significantly increased in both allergic and nonallergic sinusitis (P < 0.001). Eotaxin mRNA was expressed by nasal epithelial cells and primarily colocalized to CD68-positive macrophages within the subepithelium. In subjects with allergic rhinitis, allergen challenge markedly increased the numbers of cells expressing eotaxin mRNA and immunoreactivity in the epithelial and subepithelial cell layers (P < 0.05). This could be largely attributed to a local increase in eotaxin production within the nasal tissues. The results of this study demonstrate the constitutive expression of eotaxin and show that the numbers of cells expressing eotaxin mRNA are increased within the epithelial and subepithelial layers of the nasal mucosa in individuals with chronic sinusitis. Furthermore, allergen challenge of the nasal mucosa in atopic subjects results in a local upregulation of eotaxin expression. These data suggest a potential role for this chemokine in the pathogenesis of allergic and nonallergic eosinophilic inflammation characterizing chronic sinusitis and allergic rhinitis.
嗜酸性粒细胞趋化因子是一种嗜酸性粒细胞特异性趋化因子，与嗜酸性粒细胞募集至变应性炎症部位有关。本研究的目的是确定嗜酸性粒细胞趋化因子在患有慢性重度鼻窦炎的变应性和非变应性个体的鼻活检组织中的表达情况，并研究在变应性鼻炎患者的鼻黏膜中，变应原激发后该趋化因子的表达是否上调。我们还对表达嗜酸性粒细胞趋化因子mRNA的黏膜下层炎性细胞进行了表型分析。通过原位杂交和免疫细胞化学方法，检测了16例患有变应性或非变应性慢性鼻窦炎患者以及10例正常对照者的鼻甲组织中嗜酸性粒细胞趋化因子mRNA的存在情况和免疫反应性。在有变应性鼻炎病史的特应性受试者中，变应原或稀释剂激发后，也测定了表达嗜酸性粒细胞趋化因子mRNA的细胞数量。正常个体的鼻活检组织中存在嗜酸性粒细胞趋化因子免疫反应性的组成性表达以及嗜酸性粒细胞趋化因子mRNA阳性细胞。与正常对照相比，变应性和非变应性鼻窦炎中表达嗜酸性粒细胞趋化因子mRNA和蛋白的细胞数量均显著增加（P<0.001）。嗜酸性粒细胞趋化因子mRNA由鼻上皮细胞表达，主要与上皮下CD68阳性巨噬细胞共定位。在变应性鼻炎患者中，变应原激发显著增加了上皮和上皮下细胞层中表达嗜酸性粒细胞趋化因子mRNA和免疫反应性的细胞数量（P<０.０５）。这在很大程度上可归因于鼻组织内嗜酸性粒细胞趋化因子产生的局部增加。本研究结果证明了嗜酸性粒细胞趋化因子的组成性表达，并表明在患有慢性鼻窦炎的个体中，鼻黏膜上皮和上皮下层中表达嗜酸性粒细胞趋化因子mRNA的细胞数量增加。此外，特应性受试者鼻黏膜的变应原激发导致嗜酸性粒细胞趋化因子表达的局部上调。这些数据表明该趋化因子在以慢性鼻窦炎和变应性鼻炎为特征的变应性和非变应性嗜酸性粒细胞炎症的发病机制中可能起作用。
