Brandt E B, Zimmermann N, Muntel E E, Yamada Y, Pope S M, Mishra A, Hogan S P, Rothenberg M E
Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Clin Exp Allergy. 2006 Apr;36(4):543-53. doi: 10.1111/j.1365-2222.2006.02456.x.
Of the numerous adhesion molecules expressed by eosinophils, the alpha4-integrin has been identified as critically involved in eosinophil trafficking in the lung. Most studies have focused on the role of the alpha4beta1-adhesion complex, but eosinophils also express the alpha4beta7-integrin complex.
To investigate the role of alpha4beta7, by assessing its membrane expression on eosinophils from different compartments using allergen-challenged mice and IL-4/IL-5 bi-transgenic mice. In addition, we aim to determine the impact of beta7-integrin deficiency on eosinophil recruitment to the lungs and intestine in specific experimental allergic models.
Evaluation of alpha4beta7 expression on bronchoalveolar lavage fluid (BALF) and lung tissue eosinophils revealed a down-regulation of this integrin as eosinophils migrate through the lungs. Indeed eosinophils isolated from the BALF and lung of allergic mice had low expression of the alpha4beta7-complex. While expression of the alpha4-chain remained unchanged, a significant decrease in beta7-surface expression was observed. Intestinal eosinophils, isolated from Peyer's patches, also displayed a down-regulation of the alpha4beta7-integrin, albeit only modest. In contrast, circulating eosinophils, isolated from the blood and spleen, expressed high levels of the alpha4beta7-integrin. However, eosinophil trafficking into the lungs of beta7-integrin-deficient mice was not significantly impaired in response to respiratory allergen challenges. In contrast, beta7-deficient mice had impaired eosinophil recruitment to the intestine.
Taken together, these results identify differential expression of the alpha4beta7-integrin on eosinophils and its critical role in regulating eosinophil responses in the intestine.
在嗜酸性粒细胞表达的众多黏附分子中，α4整合素已被确定在嗜酸性粒细胞在肺中的迁移中起关键作用。大多数研究集中在α4β1黏附复合物的作用，但嗜酸性粒细胞也表达α4β7整合素复合物。
通过使用过敏原激发的小鼠和白细胞介素-4/白细胞介素-5双转基因小鼠评估不同部位嗜酸性粒细胞上α4β7的膜表达，来研究α4β7的作用。此外，我们旨在确定β7整合素缺陷在特定实验性过敏模型中对嗜酸性粒细胞向肺和肠道募集的影响。
对支气管肺泡灌洗液（BALF）和肺组织嗜酸性粒细胞上α4β7表达的评估显示，随着嗜酸性粒细胞穿过肺迁移，这种整合素表达下调。实际上，从过敏性小鼠的BALF和肺中分离出的嗜酸性粒细胞α4β7复合物表达较低。虽然α4链的表达保持不变，但观察到β7表面表达显著下降。从派伊尔结分离出的肠道嗜酸性粒细胞也显示α4β7整合素表达下调，尽管程度较轻。相比之下，从血液和脾脏中分离出的循环嗜酸性粒细胞表达高水平的α4β7整合素。然而，β7整合素缺陷小鼠肺部嗜酸性粒细胞的迁移在呼吸道过敏原激发后并未受到显著损害。相反，β7缺陷小鼠肠道嗜酸性粒细胞的募集受损。
综上所述，这些结果确定了α4β7整合素在嗜酸性粒细胞上的差异表达及其在调节肠道嗜酸性粒细胞反应中的关键作用。
