Major house dust mite allergens Dermatophagoides pteronyssinus 1 and Dermatophagoides farinae 1 degrade and inactivate lung surfactant proteins A and D
Major house dust mite allergens Dermatophagoides pteronyssinus 1 and Dermatophagoides farinae 1 degrade and inactivate lung surfactant proteins A and D
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DOI：
10.1074/jbc.m702336200
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发表时间：
2007-12-21
影响因子：
4.8
通讯作者：
Clark, Howard
中科院分区：
文献类型：
--
作者：
Deb, Roona;Shakib, Farouk;Clark, Howard
肺表面活性蛋白（SP） A和D是钙依赖性碳水化合物结合蛋白。SP-A和SP-D除了在细菌聚集和白细胞功能调节等先天免疫防御中发挥多种作用外，还与过敏反应有关。它们与广泛的吸入过敏原相互作用，与细胞隔离的IgE结合竞争，导致肥大细胞脱颗粒抑制，外源性SP-A和SP-D减少体内过敏性超敏反应。室内尘螨过敏原是西方世界过敏性哮喘的主要原因，本研究证实了SP-A和SP-D与两种主要的尘螨过敏原，Dermatophagoides pteronyssinus 1和Dermatophagoides farinae 1的相互作用，并表明这些过敏原的半胱氨酸蛋白酶活性导致SP-A和SP-D在生理条件下降解，并有多个位点的裂解。在尘螨过敏小鼠模型中有效降低过敏性超敏反应的重组SP-D片段比天然全长蛋白更容易降解。在缺乏钙的情况下，降解增强，具有不同的裂解位点，表明与SP-A和SP-D相关的钙影响对过敏原的可及性。SP-A和SP-D的降解与减少与碳水化合物和翼龙葵1本身的结合以及减少与细菌的凝集能力有关。因此，SP-A和SP-D的降解和随后的失活可能是解释这些常见尘螨过敏原的强致敏性的新机制。
Lung surfactant proteins (SP) A and D are calcium-dependent carbohydrate-binding proteins. In addition to playing multiple roles in innate immune defense such as bacterial aggregation and modulation of leukocyte function, SP-A and SP-D have also been implicated in the allergic response. They interact with a wide range of inhaled allergens, competing with their binding to cell-sequestered IgE resulting in inhibition of mast cell degranulation, and exogenous administration of SP-A and SP-D diminishes allergic hypersensitivity in vivo. House dust mite allergens are a major cause of allergic asthma in the western world, and here we confirm the interaction of SP-A and SP-D with two major mite allergens, Dermatophagoides pteronyssinus 1 and Dermatophagoides farinae 1, and show that the cysteine protease activity of these allergens results in the degradation of SP-A and SP-D under physiological conditions, with multiple sites of cleavage. A recombinant fragment of SP-D that is effective in diminishing allergic hypersensitivity in mouse models of dust mite allergy was more susceptible to degradation than the native full-length protein. Degradation was enhanced in the absence of calcium, with different sites of cleavage, indicating that the calcium associated with SP-A and SP-D influences accessibility to the allergens. Degradation of SP-A and SP-D was associated with diminished binding to carbohydrates and to D. pteronyssinus 1 itself and diminished capacity to agglutinate bacteria. Thus, the degradation and consequent inactivation of SP-A and SP-D may be a novel mechanism to account for the potent allergenicity of these common dust mite allergens.