Evidence for local eosinophil differentiation within allergic nasal mucosa: Inhibition with soluble IL-5 receptor
Evidence for local eosinophil differentiation within allergic nasal mucosa: Inhibition with soluble IL-5 receptor
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DOI：
10.4049/jimmunol.164.3.1538
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发表时间：
2000-02-01
影响因子：
4.4
通讯作者：
Hamid, Q
中科院分区：
文献类型：
--
作者：
Cameron, L;Christodoulopoulos, P;Hamid, Q
嗜酸性粒细胞分化发生在骨髓内，以响应于嗜酸性细胞因子，特别是IL-5。然而，最近，嗜酸性粒细胞前体细胞（CD 34/IL-5 R α（+）细胞）和IL-5 mRNA（+）细胞已被确定在哮喘患者的肺内，表明嗜酸性粒细胞的群体可能在原位分化。在这份报告中，我们检查了嗜酸性粒细胞前体细胞在过敏性鼻粘膜内的存在，并检查它们是否在体外刺激后发生局部分化。我们培养人鼻粘膜从个人与特异性过敏原，重组人IL-5（rhIL-5），或过敏原+可溶性IL-5 R α（sIL-5 R α），显示拮抗IL-5的功能与季节性变应性鼻炎。同时免疫细胞化学和原位杂交显示，与单独培养基相比，与变应原或rhIL-5培养后，共表达CD 34免疫反应性和IL-5 R α mRNA的细胞较少。免疫组化结果显示，过敏原或rhIL-5刺激的组织中主要碱性蛋白（MBP）免疫反应阳性细胞（嗜酸性粒细胞）的数量均高于未刺激的组织。原位杂交结果显示，过敏原刺激的组织切片中IL-5 mRNA阳性细胞的数量较单独培养的组织增加。在与变应原和sIL-5 R α组合培养的组织中未观察到这些效应。共定位分析表明，这种表达主要是，但不完全是，T细胞（44%）和嗜酸性粒细胞（10%）的衍生。我们的研究结果表明，嗜酸性粒细胞的一个子集可能会分化局部变应性鼻粘膜内，在什么似乎是一个高度IL-5依赖的方式，并意味着这一过程可能是在体内调节的内源性生产的sIL-5 R α。
Eosinophil differentiation occurs within the bone marrow in response to eosinopoietic cytokines, particularly IL-5. Recently, however, eosinophil precursors (CD34/IL-5R alpha(+) cells) and IL-5 mRNA(+) cells have been identified within the lungs of asthmatics, indicating that a population of eosinophils may differentiate in situ, In this report, we examined the presence of eosinophil precursors within allergic nasal mucosa and examined whether they undergo local differentiation following ex vivo stimulation. We cultured human nasal mucosa obtained from individuals with seasonal allergic rhinitis with either specific allergen, recombinant human IL-5 (rhIL-5), or allergen + soluble IL-5R alpha (sIL-5R alpha), shown to antagonize IL-5 function. Simultaneous immunocytochemistry and in situ hybridization demonstrated that there were fewer cells coexpressing CD34 immunoreactivity and IL-5R alpha mRNA following culture with allergen or rhIL-5, compared with medium alone. Immunostaining revealed that the number of major basic protein (MBP) immunoreactive cells (eosinophils) was higher within tissue stimulated with allergen or rhIL-5, compared with unstimulated tissue, In situ hybridization detected an increase in IL-5 mRNA+ cells in sections from tissue cultured with allergen, compared with medium alone. These effects were not observed in tissue cultured with a combination of allergen and sIL-5R alpha. Colocalization analysis indicated this expression to be mainly, but not exclusively, T cell (44%) and eosinophil (10%) derived. Our findings suggest that a subset of eosinophils may differentiate locally within allergic nasal mucosa, in what appears to be a highly IL-5-dependent fashion, and imply that this process might be regulated in vivo by endogenous production of sIL-5R alpha.