Taha R A, Minshall E M, Miotto D, Shimbara A, Luster A, Hogg J C, Hamid Q A
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
J Allergy Clin Immunol. 1999 Mar;103(3 Pt 1):476-83. doi: 10.1016/s0091-6749(99)70474-4.
Although an eosinophilic infiltrate has been observed in the small airways of asthmatic individuals, the mechanisms responsible for cellular recruitment in the lung periphery remain to be clarified. Eotaxin and monocyte chemotactic protein (MCP)-4 are 2 eosinophil-associated chemokines shown to be upregulated at sites of allergic inflammation. However, their expression within the small airways of asthmatic individuals remains to be elucidated.
We sought to determine the expression of eotaxin and MCP-4 in the peripheral airways and parenchyma of lungs of subjects with asthma and to assess their relationship to the numbers of resident eosinophils.
We examined surgically resected lung tissue from 6 asthmatic and 10 nonasthmatic subjects for the presence of eotaxin and MCP-4 mRNA by in situ hybridization. Chemokine mRNA expression was examined with respect to the numbers of eosinophils within the airways, as detected by immunocytochemistry for major basic protein.
Numbers of chemokine mRNA-positive cells were significantly increased in the large and small airways of asthmatic subjects compared with nonasthmatic subjects. Although eotaxin and MCP-4 mRNA were widely expressed in the lungs of subjects with asthma, their expression was particularly evident within the bronchial epithelium and inflammatory cells. In the airways of the asthmatic individuals, the expression of eotaxin mRNA was significantly correlated to the numbers of eosinophils present.
There is an increased expression of eotaxin and MCP-4 mRNA within the peripheral airways of lungs of asthmatic subjects, suggesting that these chemokines contribute to the small airways and peripheral lung inflammation in asthma.
虽然在哮喘患者的小气道中已观察到嗜酸性粒细胞浸润，但肺外周细胞募集的机制仍有待阐明。嗜酸性粒细胞趋化因子和单核细胞趋化蛋白（MCP）-4是两种与嗜酸性粒细胞相关的趋化因子，在变应性炎症部位显示上调。然而，它们在哮喘患者小气道中的表达仍有待阐明。
我们试图确定嗜酸性粒细胞趋化因子和MCP-4在哮喘患者肺外周气道和实质中的表达，并评估它们与驻留嗜酸性粒细胞数量的关系。
我们通过原位杂交检查了6例哮喘患者和10例非哮喘患者手术切除的肺组织中嗜酸性粒细胞趋化因子和MCP-4 mRNA的存在情况。根据通过主要碱性蛋白免疫细胞化学检测到的气道内嗜酸性粒细胞数量，检查趋化因子mRNA的表达。
与非哮喘患者相比，哮喘患者的大气道和小气道中趋化因子mRNA阳性细胞数量显著增加。虽然嗜酸性粒细胞趋化因子和MCP-4 mRNA在哮喘患者的肺中广泛表达，但其表达在支气管上皮和炎症细胞中尤为明显。在哮喘患者的气道中，嗜酸性粒细胞趋化因子mRNA的表达与存在的嗜酸性粒细胞数量显著相关。
哮喘患者肺外周气道中嗜酸性粒细胞趋化因子和MCP-4 mRNA的表达增加，表明这些趋化因子促成了哮喘中的小气道和外周肺炎症。
