Secretory protein beta-lactoglobulin in cattle stable dust may contribute to the allergy-protective farm effect.
Secretory protein beta-lactoglobulin in cattle stable dust may contribute to the allergy-protective farm effect.
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DOI：
10.1002/clt2.12125
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发表时间：
2022-03
影响因子：
4.4
通讯作者：
Jensen-Jarolim E
中科院分区：
文献类型：
--
作者：
Pali-Schöll I;Bianchini R;Afify SM;Hofstetter G;Winkler S;Ahlers S;Altemeier T;Mayerhofer H;Hufnagl K;Korath ADJ;Pranger C;Widhalm R;Hann S;Wittek T;Kasper-Giebl A;Pacios LF;Roth-Walter F;Vercelli D;von Mutius E;Jensen-Jarolim E
在养牛场长大，喝生牛奶可以预防哮喘和过敏。我们希望在这个农场效应中有一种牛特有的蛋白质作为活性成分。从牛和家禽的马厩和家庭的床垫收集灰尘。从牛身上获取尿液，并采集周围环境的气溶胶样本。样品用十二烷基硫酸钠-PAGE/免疫印迹和质谱仪进行分析，并与金属离子结合，用BLG+/−锌孵育健康献血者的PBMC，检测细胞增殖和细胞因子。给BALB/c小鼠鼻腔注射含有BLG的稳定粉尘提取物或去除BLG，观察致敏后的变态反应。来自养牛场和环境空气的灰尘中的一种主要蛋白质被确定为BLG。母牛和公牛的尿液是BLG的主要来源。在粉尘样本中，BLG与锌有关。在体外，与不含锌的载脂蛋白颗粒相比，锌颗粒对CD_4~+和CD_8~+细胞的增殖作用显著降低，而对干扰素-γ和IL-6的诱导水平显著升高。在体内，含有BLG的粉尘提取物预处理的小鼠对BLG和无关的Bet v1的过敏症状评分低于去除BLG的提取物处理前。这些体外和体内效应与内毒素无关。在牛的尿液中发现了大量的Lipocalin BLG，在牛尘样本中积累，并在农场周围被雾化。它与锌的结合有利于在体外形成人类对Th1细胞因子的细胞免疫反应。BLG与稳定粉尘中的锌一起保护小鼠免受过敏反应。BLG及其相关的配体可能以一种与生俱来的方式有助于保护过敏的农场效应。
Growing up on a cattle farm and consuming raw cow's milk protects against asthma and allergies. We expect a cattle‐specific protein as active component in this farm effect. Dust was collected from cattle and poultry stables and from mattresses of households. Urine was obtained from cattle, and ambient aerosols were sampled. Samples were analysed for BLG by SDS PAGE/immunoblot and mass spectrometry, and for association with metals by SEC‐ICP‐MS. PBMC of healthy donors were incubated with BLG +/− zinc, and proliferation and cytokines determined. BALB/c mice were pre‐treated intranasally with stable dust extract containing BLG or depleted of BLG, and subsequent allergy response after sensitization was evaluated on antibody and symptom level. A major protein in dust from cattle farms and ambient air was identified as BLG. Urine from female and male cattle is a major source of BLG. In dust samples, BLG was associated with zinc. In vitro, zinc‐BLG provoked significantly lower proliferation of CD4+ and CD8+ cells while inducing significantly higher levels of IFN‐γ and IL‐6 than the apo‐BLG devoid of zinc. In vivo, pre‐treatment of mice with dust extract containing BLG resulted in lower allergy symptom scores to BLG and unrelated Bet v 1 than pre‐treatment with extract depleted of BLG. These in vitro and in vivo effects were independent of endotoxin. The lipocalin BLG is found in large amounts in cattle urine, accumulates in bovine dust samples and is aerosolized around farms. Its association with zinc favorably shapes the human cellular immune response towards Th1‐cytokines in vitro. BLG together with zinc in stable dust protects mice from allergic sensitization. BLG with its associated ligands may in an innate manner contribute to the allergy‐protective farm effect.
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影响因子：
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作者：
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