House dust mite Der p 1 downregulates defenses of the lung by inactivating elastase inhibitors
House dust mite Der p 1 downregulates defenses of the lung by inactivating elastase inhibitors
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DOI：
10.1165/rcmb.2003-0060oc
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发表时间：
2003-09-01
影响因子：
6.4
通讯作者：
Sallenave, JM
中科院分区：
文献类型：
--
作者：
Brown, A;Farmer, K;Sallenave, JM
屋尘螨（HDM）是最常见的空气过敏原来源，在遗传易感个体中可引起从特应性皮炎到支气管哮喘的症状。Der p 1是人类对HDM的免疫应答的主要靶标，通过其酶性质可以通过切割CD 23和CD 25来调节适应性免疫系统。这样做的后果将是促进过敏性炎症反应。此外，通过破坏上皮紧密连接，Der p 1促进过敏原穿过上皮的运输。在这里，我们报告Der p 1通过体外和离体灭活弹性蛋白酶抑制剂人（h）α 1-蛋白酶抑制剂（h-A1-Pi）、小鼠（m-）（但不是人[h]）-SLPI和h-弹性蛋白酶，对肺的先天防御机制具有额外的作用。我们证实，Der p 1包含半胱氨酸和丝氨酸蛋白酶，并扩展这一发现首次证明，h-弹力蛋白是特别敏感的后者的生物活性。由于这些弹性蛋白酶抑制剂具有抗菌活性和抗弹性蛋白酶活性，我们的研究结果表明，Der p 1使肺部防御系统的这些先天成分失活可能会增加过敏性炎症患者对感染的易感性。
House dust mites (HDM) are the most common source of aero-allergens and in genetic susceptible individuals can cause symptoms ranging from atopic dermatitis to bronchial asthma. Der p 1, a major target of the human immune responses to HDM, through its enzymatic properties can modulate the adaptive immune system by the cleavage of CD23 and CD25. The consequences of this would be to promote allergic inflammatory responses. Furthermore, by disrupting epithelial tight junctions Der p 1 facilitates the transport of allergen across the epithelium. Here, we report that Der p 1 has additional effects on the innate defense mechanisms of the lung, by inactivating in vitro and ex vivo the elastase inhibitors human (h) alpha1-proteinase inhibitor (h-A1-Pi), mouse (m-), (but not human [h])-SLPI and h-elafin. We confirm that Der p 1 contain both cysteine and serine proteinases, and extend this finding to demonstrate for the first time that h-elafin is particularly sensitive to the biological activity of the latter. Because these elastase inhibitors have antimicrobial, as well as antielastase activity, our results suggest that inactivation of these innate components of the lung defense system by Der p 1 may increase the susceptibility of patients with allergic inflammation to infection.