IL-4 controls the selective endothelium-driven transmigration of eosinophils from allergic individuals.
IL-4 controls the selective endothelium-driven transmigration of eosinophils from allergic individuals.
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IL-4 控制过敏个体中选择性内皮驱动的嗜酸性粒细胞迁移。
DOI：
10.4049/jimmunol.149.4.1432
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发表时间：
1992
影响因子：
4.4
通讯作者：
P. Bruijnzeel
中科院分区：
文献类型：
--
作者：
René Moser;J. Fehr;P. Bruijnzeel
导致嗜酸性粒细胞在过敏性发炎组织中选择性积聚的机制仍不清楚。在本文中，通过在人成纤维细胞的细胞外基质上培养的人脐静脉内皮细胞来表征来自正常和过敏个体的循环嗜酸性粒细胞的跨内皮迁移。 IL-4 对这些血管结构的预处理诱导了嗜酸性粒细胞的粘附和令人印象深刻的层渗透，但不诱导中性粒细胞。为了进行层渗透，来自非过敏性供体的血液嗜酸性粒细胞需要通过粒细胞/巨噬细胞-CSF、IL-3或IL-5进行体外启动。相比之下，从一组特应性皮炎患者中新鲜分离的血液嗜酸性粒细胞自发穿透 IL-4 激活的血管结构。这里描述的嗜酸性粒细胞迁移的选择性途径是1)由IL-4特异性诱导的； 2) 被 IL-4 特异性中和 mAb 8F12 抑制； 3) 依赖于内皮 mRNA 合成。 IL-4 浓度为 1 U/ml 时，嗜酸性粒细胞粘附和迁移均存在。内皮细胞与 IL-4 预孵育的效果在 16 小时时达到顶峰，并持续长达 48 小时。 2小时内观察到内皮下累积的嗜酸性粒细胞线性增加，共孵育4小时后几乎达到100%。从使用不同 mAb 的抑制实验中，我们得出结论，整合素 CD11a/CD18、CD11b/CD18 和非常晚期的 Ag-4 (CDw49d/CD29) 参与了嗜酸性粒细胞迁移的这种选择性途径。总而言之，这项研究证明了一种新的机制，允许体外或体内引发的嗜酸性粒细胞离开血管室而不影响中性粒细胞的迁移。
The mechanism leading to selective accumulation of eosinophils in allergic inflamed tissue is still unknown. In this article, transendothelial migration of circulating eosinophils from normal and allergic individuals is characterized by means of human umbilical vein endothelial cells cultivated on extracellular matrix from human fibroblasts. IL-4 pretreatment of these vascular constructs induced adherence and impressive layer penetration of eosinophils but not of neutrophils. For layer penetration, blood eosinophils from nonallergic donors needed in vitro priming by granulocyte/macrophage-CSF, IL-3, or IL-5. In contrast, freshly isolated blood eosinophils from a group of patients with atopic dermatitis spontaneously penetrated IL-4-activated vascular constructs. The here described selective pathway of eosinophil transmigration was 1) specifically induced by IL-4; 2) inhibited by the IL-4 specific, neutralizing mAb 8F12; and 3) dependent upon endothelial mRNA synthesis. Both eosinophil adherence and transmigration were present at an IL-4 concentration of 1 U/ml. The effect of endothelial preincubation with IL-4 culminated at 16 h and persisted up to 48 h. A linear increase of subendothelial accumulating eosinophils was observed within 2 h, reaching almost 100% after 4 h of coincubation. From inhibition experiments using different mAb, we conclude that the integrins CD11a/CD18, CD11b/CD18, and very late Ag-4 (CDw49d/CD29) are involved in this selective pathway of eosinophil transmigration. Taken together, this study demonstrates a novel mechanism which allows in vitro or in vivo primed eosinophils to leave the vascular compartment without influencing emigration of neutrophils.