周细胞
哮喘
血管生成
肥大细胞
蛋白酵素
免疫学
病理
肺
屋尘螨
类胰蛋白酶
微循环
病理生理学
医学
内皮干细胞
过敏
生物
癌症研究
内科学
体外
酶
生物化学
过敏原
作者
Régis Joulia,Franz Puttur,Helen Stölting,William J. Traves,Lewis J. Entwistle,А. Н. Войтович,Minerva Garcia Martín,May Al-Sahaf,Katie Bonner,Elizabeth Scotney,Philip L. Molyneaux,Ronna Hewitt,Simone A. Walker,Laura L. Yates,Sejal Saglani,Clare M. Lloyd
摘要
Allergic asthma generally starts during early life and is linked to substantial tissue remodeling and lung dysfunction. Although angiogenesis is a feature of the disrupted airway, the impact of allergic asthma on the pulmonary microcirculation during early life is unknown. Here, using quantitative imaging in precision-cut lung slices (PCLSs), we report that exposure of neonatal mice to house dust mite (HDM) extract disrupts endothelial cell/pericyte interactions in adventitial areas. Central to the blood vessel structure, the loss of pericyte coverage was driven by mast cell (MC) proteases, such as tryptase, that can induce pericyte retraction and loss of the critical adhesion molecule N-cadherin. Furthermore, spatial transcriptomics of pediatric asthmatic endobronchial biopsies suggests intense vascular stress and remodeling linked with increased expression of MC activation pathways in regions enriched in blood vessels. These data provide previously unappreciated insights into the pathophysiology of allergic asthma with potential long-term vascular defects.
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