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首页> 外文期刊>Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society >Altered eosinophil profile in mice with ST6Gal-1 deficiency: an additional role for ST6Gal-1 generated by the P1 promoter in regulating allergic inflammation
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Altered eosinophil profile in mice with ST6Gal-1 deficiency: an additional role for ST6Gal-1 generated by the P1 promoter in regulating allergic inflammation

机译：ST6Gal-1缺乏症小鼠的嗜酸性粒细胞谱改变：P1启动子产生的ST6Gal-1在调节变应性炎症中的其他作用

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Cumulative evidence indicates that the sialyltransferase ST6Gal-1 and the sialyl-glycans, which it constructs, are functionally pleiotropic. Expression of the ST6Gal-1 gene is mediated by six distinct promoter/regulatory regions, and we hypothesized that these promoters may be used differentially to produce ST6Gal-1 for different biologic purposes. To examine this hypothesis, we compared a mouse with a complete deficiency in ST6Gal-1 (Siat1 null) with another mouse that we have created previously with a disruption only in the P1 promoter (Siat1?”P1). We noted previously greater neutrophilic inflammation associated with ST6Gal-1 deficiency. Here, we report that ST6Gal-1-deficient mice also have significantly elevated eosinophilic responses. Upon i.p. thioglycollate elicitation, eosinophils accounted for over 20% of the total peritoneal inflammatory cell pool in ST6Gal-1-deficient animals, which was threefold greater than in corresponding wild-type animals. A principal feature of allergic respiratory inflammation is pulmonary eosinophilia, we evaluated the role of ST6Gal-1 in allergic lung inflammation. Using OVA and ABPA experimental models of allergic airways, we showed that ST6Gal-1 deficiency led to greater airway inflammation characterized by excessive airway eosinophilia. The severity of airway inflammation was similar between Siat1?”P1 and Siat1 null mice, indicating a role for P1-generated ST6Gal-1 in regulating eosinophilic inflammation. Colony-forming assays suggested greater IL-5-dependent eosinophil progenitor numbers in the marrow of ST6Gal-1-deficient animals. Moreover, allergen provocation of wild-type mice led to a significant reduction in P1-mediated ST6Gal-1 mRNA and accompanied decline in circulatory ST6Gal-1 levels. Taken together, the data implicate ST6Gal-1 as a participant in regulating not only Th1 but also Th2 responses, and ST6Gal-1 deficiency can lead to the development of more severe allergic inflammation with excessive eosinophil production.
机译：累积证据表明，它构建的唾液酸转移酶ST6Gal-1和唾液酸聚糖在功能上是多效的。 ST6Gal-1基因的表达是由六个不同的启动子/调控区介导的，我们假设这些启动子可以不同地用于产生ST6Gal-1，以用于不同的生物学目的。为了检验这一假设，我们将ST6Gal-1完全缺乏的小鼠（Siat1为空）与我们先前创建的仅在P1启动子中具有破坏的另一只小鼠（Siat1？” P1）进行了比较。我们先前注意到与ST6Gal-1缺乏症相关的更大的嗜中性粒细胞炎症。在这里，我们报告ST6Gal-1缺陷小鼠也有明显升高的嗜酸性反应。在i.p.在硫代乙醇酸酯的激发下，嗜酸性粒细胞占ST6Gal-1缺陷动物腹膜炎性细胞总数的20％以上，是相应野生型动物的三倍。过敏性呼吸道炎症的主要特征是肺嗜酸性粒细胞增多，我们评估了ST6Gal-1在过敏性肺炎症中的作用。使用OVA和ABPA过敏性气道实验模型，我们显示ST6Gal-1缺乏症导致以气道嗜酸性粒细胞增多为特征的更大的气道炎症。 Siat1？” P1和Siat1缺失小鼠之间的气道炎症严重程度相似，表明P1生成的ST6Gal-1在调节嗜酸性粒细胞炎症中具有作用。集落形成试验表明在ST6Gal-1缺陷动物的骨髓中IL-5依赖性嗜酸性粒细胞祖细胞数目增加。此外，野生型小鼠的过敏原激发导致P1介导的ST6Gal-1 mRNA显着降低，并伴随循环ST6Gal-1水平下降。两者合计，数据暗示ST6Gal-1不仅参与调节Th1响应，而且参与调节Th2响应，而ST6Gal-1缺乏则可能导致嗜酸性粒细胞过多而引起更严重的过敏性炎症。

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