哮喘联盟

   摘要
   哮喘是一种常见的疾病，全世界有>250百万的患者。表现为对炎症介质（包括乙酰胆碱Ach、缓激肽和组胺等）的过度支气管收缩，也定义为气道高反应性。接近10%的哮喘患者表现为重型，并存在治疗抵抗现象，该部分患者通常与普遍存在的真菌（特别是烟曲霉菌）致敏性IgE相关。Asp f13是一种主要的烟曲霉菌致敏原，属于丝氨酸蛋白酶，碱性蛋白酶1（Alp 1）。本研究表明其可能通过浸润支气管粘膜下层和破坏气道平滑肌（ASM）细胞与细胞外基质（ECM）相互作用促进气道的高反应性。碱性蛋白酶1介导的细胞外基质降解可引起病理生理性RhoA依赖的Ca(2+)敏感性以及支气管收缩。本研究结果提示，对于哮喘患者以及其它上皮屏障受损性肺病，气道平滑肌细胞直接与吸入性环境中的过敏原接触导致气道高反应性可能是该类疾病的一种可能致病机制。
 

（杨冬 审校）
Nat Commun. 2015 Apr 13;6:6763. doi: 10.1038/ncomms7763.
 

A fungal protease allergen provokes airway hyper-responsiveness in asthma.
 

Balenga NA1, Klichinsky M2, Xie Z1, Chan EC1, Zhao M3, Jude J2, Laviolette M4, Panettieri RA Jr2, Druey KM1.

Author information
 

Abstract
Asthma, a common disorder that affects >250 million people worldwide, is defined by exaggerated bronchoconstriction to inflammatory mediators including acetylcholine (ACh), bradykinin and histamine-also termed airway hyper-responsiveness. Nearly 10% of people with asthma have severe, treatment-resistant disease, which is frequently associated with immunoglobulin-E sensitization to ubiquitous fungi, typically Aspergillus fumigatus (Af). Here we show that a major Af allergen, Asp f13, which is a serine protease, alkaline protease 1 (Alp 1), promotes airway hyper-responsiveness by infiltrating the bronchial submucosa and disrupting airway smooth muscle (ASM) cell-extracellular matrix (ECM) interactions. Alp 1-mediated ECM degradation evokes pathophysiological RhoA-dependent Ca(2+) sensitivity and bronchoconstriction. These findings support a pathogenic mechanism in asthma and other lung diseases associated with epithelial barrier impairment, whereby ASM cells respond directly to inhaled environmental allergens to generate airway hyper-responsiveness.
 

Nat Commun. 2015 Apr 13;6:6763. doi: 10.1038/ncomms7763.