Subpollen particles: Carriers of allergenic proteins and oxidases
Subpollen particles: Carriers of allergenic proteins and oxidases
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DOI：
10.1016/j.jaci.2006.07.006
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发表时间：
2006-10-01
影响因子：
14.2
通讯作者：
Boldogh, Istvan
中科院分区：
文献类型：
--
作者：
Bacsi, Attila;Choudhury, Barun K.;Boldogh, Istvan
工作背景：众所周知，花粉会诱发特应性个体的过敏性哮喘，尽管只有少数吸入的花粉粒会渗透到下呼吸道。目的：我们试图提供证据表明，具有抗原性和氧化还原性的可吸入大小的亚花粉颗粒（SPP）从杂草花粉中释放出来，并测试它们在过敏性气道炎症中的作用。方法：通过显微成像和流式细胞术分析SPPs的释放。用氧化还原敏感探针和特异性抑制剂测定了SPP的氧化还原特性和SPP介导的上皮细胞氧化效应。Western blotting和氨基酸序列分析对SPP的蛋白组分进行了分析。在实验asthma.Results的小鼠模型中测定了SPP的致敏特性：豚草花粉粒在水合作用下释放0.5至4.5 μ m的SPP。它们含有Amb a 1，沿着豚草花粉的其它变应原蛋白，并具有烟酰胺腺嘌呤二核苷酸（还原）或烟酰胺腺嘌呤二核苷酸磷酸（还原）[NAD（P）H]氧化酶活性。SPPs显著增加培养细胞中活性氧（ROS）的水平，并诱导实验动物的过敏性气道炎症。用NAD（P）H氧化酶抑制剂预处理SPPs减弱了它们增加气道上皮细胞ROS水平和随后的气道炎症的能力。结论：豚草花粉粒释放的SPPs的致敏效力是由内源性NAD（P）H氧化酶和抗原蛋白产生的ROS串联介导的。临床意义：与季节性哮喘相关的严重临床症状可能是对吸入的携带变应原蛋白和ROS产生的NAD（P）H氧化酶的SPP的免疫应答。
Background: Pollen is known to induce allergic asthma in atopic individuals, although only a few inhaled pollen grains penetrate into the lower respiratory tract.Objective: We sought to provide evidence that subpollen particles (SPPs) of respirable size, possessing both antigenic and redox properties, are released from weed pollen grains and to test their role in allergic airway inflammation.Methods: The release of SPPs was analyzed by means of microscopic imaging and flow cytometry. The redox properties of SPPs and the SPP-mediated oxidative effect on epithelial cells were determined by using redox-sensitive probes and specific inhibitors. Western blotting and amino acid sequence analysis were used to examine the protein components of the SPP. The allergenic properties of the SPP were determined in a murine model of experimental asthma.Results: Ragweed pollen grains released 0.5 to 4.5 mu m of SPPs on hydration. These contained Amb a 1, along with other allergenic proteins of ragweed pollen, and possessed nicotinamide adenine dinucleotide (reduced) or nicotinamide adenine dinucleotide phosphate (reduced) [NAD(P)H] oxidase activity. The SPPs significantly increased the levels of reactive oxygen species (ROS) in cultured cells and induced allergic airway inflammation in the experimental animals. Pretreatment of the SPPs with NAD(P)H oxidase inhibitors attenuated their capacity to increase ROS levels in the airway epithelial cells and subsequent airway inflammation.Conclusions: The allergenic potency of SPPs released from ragweed pollen grains is mediated in tandem by ROS generated by intrinsic NAD(P)H oxidases and antigenic proteins.Clinical implications: Severe clinical symptoms associated with seasonal asthma might be explained by immune responses to inhaled SPPs carrying allergenic proteins and ROS-producing NAD(P)H oxidases.