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首页> 外文期刊>Allergy >Luminal decoration of blood vessels by activated perivasal mast cells in allergic rhinitis
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Luminal decoration of blood vessels by activated perivasal mast cells in allergic rhinitis

机译：变应性鼻炎中激活的血管周围肥大细胞对血管的发光修饰

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Background In allergic diseases, like in rhinitis, antigen challenge induces rapid degranulation of tissue resident mast cells and subsequent recruitment of leukocytes in response to soluble immunmodulators. The fate of mast cell-derived, membrane associated factors in inflamed tissue remained however unresolved. Methods Components of the mast cell granular membrane, including the unique marker CD63var, were examined by FACS and by confocal laser scanning microscopy in cell culture and in diseased human tissue. Results We discovered that selected mast cell membrane components appeared on the surface of distinct bystander cells. Acceptor cells did not acquire these molecules simply by uptake of soluble material or in the form of exosomes. Instead, physically stable cell-to-cell contact was required for transfer, in which a Notch2-Jagged1 interaction played a decisive role. This process is activation-dependent, unidirectional, and involves a unique membrane topology. Endothelial cells were particularly efficient acceptors. In organotypic 3D in vitro cultures we found that transferred mast cell molecules traversed an endothelial monolayer, and reappeared focally compacted on its distal surface, away from the actual contact zone. Moreover, we observed that such mast cell-derived membrane patches decorate microcapillaries in the nasal mucosa of allergic rhinitis patients. Conclusion Direct membrane transfer from perivasal mast cells into nearby blood vessels constitutes a novel mechanism to modulate endothelial surface features with apparent significance in allergic diseases.
机译：背景技术在变态反应性疾病中，例如在鼻炎中，抗原攻击会诱导组织常驻肥大细胞快速脱粒，并随后响应可溶性免疫调节剂募集白细胞。肥大细胞源性，膜相关因子在发炎组织中的命运仍未得到解决。方法通过流式细胞仪和共聚焦激光扫描显微镜检查肥大细胞颗粒膜的成分，包括独特的标记CD63var，用于细胞培养和患病人体组织中。结果我们发现选定的肥大细胞膜成分出现在不同旁观者细胞的表面。受体细胞不能仅仅通过吸收可溶性物质或外来体的形式来获得这些分子。相反，转移需要物理上稳定的细胞间接触，其中Notch2-Jagged1相互作用起决定性作用。该过程是活化依赖性的，单向的，并且涉及独特的膜拓扑。内皮细胞是特别有效的受体。在器官型3D体外培养中，我们发现转移的肥大细胞分子穿过内皮单层，并在远离实际接触区域的地方重新集中出现在其远端表面。此外，我们观察到这种肥大细胞衍生的膜片可修饰变应性鼻炎患者鼻黏膜中的微毛细血管。结论膜直接从血管周围肥大细胞转移至附近血管构成了一种调节内皮表面特征的新机制，在过敏性疾病中具有明显意义。

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