Ouyang Xuan, Reihill James A, Douglas Lisa E J, Martin S Lorraine
School of Pharmacy, Queen's University Belfast, Belfast, UK.
School of Pharmacy, Queen's University Belfast, Belfast, UK
Eur Respir Rev. 2024 Apr 24;33(172). doi: 10.1183/16000617.0126-2023. Print 2024 Apr 30.
Common airborne allergens (pollen, animal dander and those from fungi and insects) are the main triggers of type I allergic disorder in the respiratory system and are associated with allergic rhinitis, allergic asthma, as well as immunoglobulin E (IgE)-mediated allergic bronchopulmonary aspergillosis. These allergens promote IgE crosslinking, vasodilation, infiltration of inflammatory cells, mucosal barrier dysfunction, extracellular matrix deposition and smooth muscle spasm, which collectively cause remodelling of the airways. Fungus and insect (house dust mite and cockroaches) indoor allergens are particularly rich in proteases. Indeed, more than 40 different types of aeroallergen proteases, which have both IgE-neutralising and tissue-destructive activities, have been documented in the Allergen Nomenclature database. Of all the inhaled protease allergens, 85% are classed as serine protease activities and include trypsin-like, chymotrypsin-like and collagenolytic serine proteases. In this article, we review and compare the allergenicity and proteolytic effect of allergen serine proteases as listed in the Allergen Nomenclature and MEROPS databases and highlight their contribution to allergic sensitisation, disruption of the epithelial barrier and activation of innate immunity in allergic airways disease. The utility of small-molecule inhibitors of allergen serine proteases as a potential treatment strategy for allergic airways disease will also be discussed.
常见的空气传播过敏原（花粉、动物皮屑以及来自真菌和昆虫的过敏原）是呼吸系统I型过敏疾病的主要触发因素，与过敏性鼻炎、过敏性哮喘以及免疫球蛋白E（IgE）介导的过敏性支气管肺曲霉病相关。这些过敏原会促进IgE交联、血管舒张、炎症细胞浸润、黏膜屏障功能障碍、细胞外基质沉积和平滑肌痉挛，共同导致气道重塑。真菌和昆虫（屋尘螨和蟑螂）室内过敏原尤其富含蛋白酶。实际上，变应原命名数据库中已记录了40多种具有IgE中和及组织破坏活性的不同类型的气传变应原蛋白酶。在所有吸入性蛋白酶变应原中，85%归类为丝氨酸蛋白酶活性，包括胰蛋白酶样、糜蛋白酶样和胶原分解丝氨酸蛋白酶。在本文中，我们回顾并比较了变应原命名数据库和MEROPS数据库中列出的变应原丝氨酸蛋白酶的致敏性和蛋白水解作用，并强调它们在过敏性气道疾病中对过敏致敏、上皮屏障破坏和先天免疫激活的作用。还将讨论变应原丝氨酸蛋白酶小分子抑制剂作为过敏性气道疾病潜在治疗策略的效用。
