Kotsimbos T C, Ghaffar O, Minshall E M, Humbert M, Durham S R, Pfister R, Menz G, Kay A B, Hamid Q A
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
J Allergy Clin Immunol. 1998 Nov;102(5):859-66. doi: 10.1016/s0091-6749(98)70029-6.
Recent studies have provided evidence for increased IL-4 expression in the airways of atopic and nonatopic asthmatic subjects. IL-4 is believed to perform important regulatory roles in asthma; however, the expression of the IL-4 receptor has not been investigated. In this study we examined the mRNA and protein expression of the specific alpha-subunit of the IL-4 receptor (alphaIL-4R) in bronchial biopsy specimens obtained from atopic and nonatopic asthmatic subjects.
Asthmatic subjects and nonasthmatic control subjects were recruited, and lung function measurements were performed before bronchoscopy. Endobronchial biopsy specimens were examined for the presence of alphaIL-4R mRNA and immunoreactivity by using in situ hybridization and immunocytochemistry, respectively.
alphaIL-4R mRNA-positive and immunoreactive cells were detected in the epithelium and subepithelium in biopsy specimens from all subjects. Expression of alphaIL-4R mRNA and protein was significantly increased in the epithelium and subepithelium of biopsy specimens from atopic asthmatic subjects compared with atopic control subjects (P <.05 and P <.001, respectively). Epithelial alphaIL-4R mRNA expression and immunoreactivity did not differ significantly between nonatopic asthmatic subjects and nonatopic control subjects. Although the numbers of alphaIL-4R mRNA-positive cells were augmented in the submucosa of intrinsic asthmatic subjects compared with nonatopic control subjects (P <.05), alphaIL-4R immunoreactivity did not differ significantly between these groups. Increased alphaIL-4R immunoreactive signals were also detected in the endothelial cell layer in both atopic and intrinsic asthmatic subjects compared with atopic and nonatopic control subjects, respectively (P <.05). Combined in situ hybridization immunocytochemistry performed on biopsy sections from asthmatic and control subjects demonstrated alphaIL-4R mRNA expression in CD3-positive T cells and tryptasepositive mast cells, with T cells comprising the larger proportion of alphaIL-4R mRNA-positive cells. Numbers of alphaIL-4R mRNA-positive or immunoreactive cells did not correlate with CD3-positive cell numbers, numbers of IL-4 mRNA-positive cells, or indices of pulmonary function.
These results demonstrate constitutive alphaIL-4R expression in normal airways and enhanced expression in airway tissue from asthmatic individuals.
近期研究已证实特应性和非特应性哮喘患者气道中白细胞介素-4（IL-4）表达增加。IL-4被认为在哮喘中发挥重要调节作用；然而，IL-4受体的表达尚未得到研究。在本研究中，我们检测了从特应性和非特应性哮喘患者获取的支气管活检标本中IL-4受体特异性α亚基（αIL-4R）的mRNA和蛋白表达。
招募哮喘患者和非哮喘对照者，在支气管镜检查前进行肺功能测量。分别使用原位杂交和免疫细胞化学检测支气管活检标本中αIL-4R mRNA的存在及免疫反应性。
在所有受试者的活检标本上皮和上皮下均检测到αIL-4R mRNA阳性和免疫反应性细胞。与特应性对照者相比，特应性哮喘患者活检标本上皮和上皮下αIL-4R mRNA和蛋白表达显著增加（分别为P<.05和P<.001）。非特应性哮喘患者与非特应性对照者之间上皮αIL-4R mRNA表达和免疫反应性无显著差异。虽然与非特应性对照者相比，内源性哮喘患者黏膜下层αIL-4R mRNA阳性细胞数量增加（P<.05），但这些组之间αIL-4R免疫反应性无显著差异。与特应性和非特应性对照者相比，在特应性和内源性哮喘患者的内皮细胞层中也分别检测到αIL-4R免疫反应信号增加（P<.05）。对哮喘患者和对照者活检切片进行的联合原位杂交免疫细胞化学显示，αIL-4R mRNA在CD3阳性T细胞和类胰蛋白酶阳性肥大细胞中表达，其中T细胞占αIL-4R mRNA阳性细胞的比例更大。αIL-4R mRNA阳性或免疫反应性细胞数量与CD3阳性细胞数量、IL-4 mRNA阳性细胞数量或肺功能指标均无相关性。
这些结果表明正常气道中存在组成性αIL-4R表达，且哮喘个体气道组织中表达增强。
