The Open Allergy Journal最新文献_第3页

HRF-Interacting Molecules HRF-Interacting分子

The Open Allergy Journal

Pub Date : 2012-05-18 DOI: 10.2174/1874838401205010041

T. Kawakami, T. Ando, Y. Kawakami

Histamine-releasing factor (HRF), also termed translationally controlled tumor protein (TCTP) and fortilin, is a highly conserved, multi-functional protein. This protein within a cell plays a critical role in the fundamental processes of cell-cycle progression, proliferation, survival, and malignant transformation. The same protein, despite the lack of signal sequence, is secreted through a nonclassical secretory pathway. The secreted protein usually termed HRF can activate IgE-primed basophils and mast cells, and works as a B cell growth factor and a chemoattractant for eosinophils. This structurally well-characterized protein interacts with many proteins to perform its intracellular and extracellular functions. This review summarizes recent studies of HRF/TCTP-interacting proteins as a major driving force to decipher its functions.

组胺释放因子(Histamine-releasing factor, HRF)，又称翻译控制肿瘤蛋白(translation controlled tumor protein, TCTP)和fortilin，是一种高度保守的多功能蛋白。这种蛋白在细胞周期进程、增殖、存活和恶性转化的基本过程中起着关键作用。同样的蛋白质，尽管缺乏信号序列，通过非经典分泌途径分泌。通常被称为HRF的分泌蛋白可以激活ige引发的嗜碱性细胞和肥大细胞，并作为B细胞生长因子和嗜酸性细胞的化学引诱剂。这种结构特征良好的蛋白质与许多蛋白质相互作用，以执行其细胞内和细胞外功能。本文综述了近年来有关HRF/ tcpp相互作用蛋白的研究，并将其作为破译其功能的主要驱动力。

引用次数: 6

On the Mechanisms Underlying the Secretion and Export of Translationally Controlled Tumor Protein/Histamine Releasing Factor (TCTP/HRF) 翻译控制肿瘤蛋白/组胺释放因子(TCTP/HRF)分泌和输出的机制研究

The Open Allergy Journal

Pub Date : 2012-05-18 DOI: 10.2174/1874838401205010033

J. Maeng, Miyoung Kim, Kyunglim Lee

Numerous studies have demonstrated that TCTP/HRF is a unique cytokine, modulating the release of inflammatory mediators from various cell types including cells involved in allergic phenomena. Despite the absence of a leader sequence in its NH2-terminus, TCTP/HRF is regarded as a secreted protein found outside of cells as well as in fluids from allergic patients and parasitic organisms. Recent studies clarified several potential mechanisms leading to its secretion. For example, these studies showed that TCTP/HRF is exported from cells via a non-classical, endoplasmic reticulum (ER)/Golgi-independent mechanism associated with exosomal transport. TSAP6, a p53-inducible transmembrane protein, has been shown to enhance exosome production, and facilitate the secretion of TCTP/HRF into extracellular milieu. Additionally, H,K-ATPase also appears to play a role in the transport of TCTP/HRF, since inhibitors of H,K-ATPase also inhibit TCTP/HRF exit. The exact mechanisms involved in TCTP/HRF secretion has not yet emerged. Here we attempted to collate the available information in the current understanding of the mechanisms underlying the release of TCTP/HRF and of the factors that seem to influence these mechanisms.

大量研究表明，TCTP/HRF是一种独特的细胞因子，可以调节各种细胞类型的炎症介质的释放，包括参与过敏现象的细胞。尽管在其nh2端缺乏先导序列，TCTP/HRF被认为是一种分泌蛋白，存在于细胞外以及过敏患者和寄生生物的体液中。最近的研究阐明了导致其分泌的几种潜在机制。例如，这些研究表明，TCTP/HRF通过与外泌体运输相关的非经典内质网(ER)/高尔基非依赖性机制从细胞输出。TSAP6是一种p53诱导的跨膜蛋白，已被证明可以促进外泌体的产生，并促进TCTP/HRF分泌到细胞外环境。此外，H, k - atp酶似乎也在TCTP/HRF的转运中发挥作用，因为H, k - atp酶的抑制剂也抑制TCTP/HRF的退出。TCTP/HRF分泌的确切机制尚不清楚。在这里，我们试图整理现有的关于tcp /HRF释放机制和影响这些机制的因素的信息。

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引用次数: 2

Positive Correlation Between Japanese Cedar Pollen Numbers and the Development of Kawasaki Disease 杉木花粉数量与川崎病发生的正相关研究

The Open Allergy Journal

Pub Date : 2012-05-04 DOI: 10.2174/1874838401205010001

A. Awaya, Koji Murayama

Objective: Kawasaki disease (KD), an acute febrile disease that induces systemic vasculitis in infants, has been proposed by Awaya and Sahashi in 2003 to be epidemiologically linked with pollen exposure. In this report, seasonal variation patterns of the monthly development of KD in 5,917 patients (Pt.) in Kanagawa, Japan were compared with the monthly pollen release numbers (Nos.) from 1991 to 2002. Methodology: A correlation coefficient (c.c.) matrix was gen- erated using regression analyses of the correlation of KD onset and pollen exposure in each month. The percent of Japa- nese cedar pollen Nos. was calculated from the pollen numbers (Po.Nos.) of all the species surveyed in March and April throughout the years. Results: Significant c.c. associations were revealed between Po.Nos. from all species in March and KD Pt.Nos. in August (0.88), November (0.72), May (0.68), and April (0.66). Significant c.c. associations were also found between Po.Nos. from all species in April and KD Pt.Nos. in August (0.70), and between Po.Nos from all species in Feb- ruary and KD Pt.Nos. in July (0.62). Mean c.c. values of 0.60 in March, 0.47 in October, 0.45 in July, 0.35 in April, and 0.31 in February between Po.Nos. and KD Pt.Nos. were shown. February, March and April contributed 4.7%, 40.6% and 38.8% of the annual Po.Nos., respectively, of which 93.8%, 84.3% and 10.9% were from cedar pollen, respectively. Conclusions: A positive association was demonstrated between the Po.Nos. from all species, particularly cedar Po.Nos. in March, and the KD Pt.Nos. in the following several months.

目的:川崎病(Kawasaki disease, KD)是一种引起婴儿全身性血管炎的急性发热性疾病，Awaya和Sahashi在2003年提出与花粉暴露有流行病学联系。本文对1991 ~ 2002年日本神奈川县5917例患者(Pt.)的花粉月释放数(no .)与KD月发展的季节变化进行了比较。方法:采用相关系数(c.c)矩阵对每个月KD发病与花粉暴露的相关性进行回归分析。杉木花粉数的百分比是根据历年3月和4月调查树种的花粉数(Po.Nos)计算得出的。结果:po . no .之间存在显著的c.c.相关性。3月份，所有物种和KD ptno。8月(0.88)、11月(0.72)、5月(0.68)、4月(0.66)。在po . no .之间也发现了显著的cc关联。4月份，所有物种和KD pno . 1。8月(0.70);2月至2月间所有物种的编号及KD的编号。7月(0.62)。3月、10月、7月、4月、2月的平均c.c.值分别为0.60、0.47、0.45、0.35和0.31。和KD p . no .;被显示。2月、3月和4月分别占全年进口量的4.7%、40.6%和38.8%。，其中杉木花粉含量分别为93.8%、84.3%和10.9%。结论:po、no、no之间存在正相关。所有物种，尤其是雪松。在3月份，而KD的pno。在接下来的几个月里。

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引用次数: 12

Heating Affects Structure, Enterocyte Adsorption and Signalling, As Well as Immunogenicity of the Peanut Allergen Ara h 2. 加热影响花生过敏原Ara h2的结构、肠细胞吸附和信号传导以及免疫原性。

The Open Allergy Journal

Pub Date : 2011-12-09 DOI: 10.2174/1874838401104010024

Philipp Starkl, Durga Krishnamurthy, Krisztina Szalai, Ferdinand Felix, Anna Lukschal, Dominik Oberthuer, Hugh A Sampson, Ines Swoboda, Christian Betzel, Eva Untersmayr, Erika Jensen-Jarolim

Previous studies have indicated that specific molecular properties of proteins may determine their allergenicity. Allergen interaction with epithelia as the first contact site could be decisive for a resulting immune response. We investigate here for the major peanut allergen Ara h 2 whether thermal processing results in structural changes which may impact the protein's molecular interactions with enterocytes, subsequent cellular signalling response, and immunogenicity.Ara h 2 was heat processed and analyzed in terms of patient IgE binding, structural alterations, interaction with human enterocytes and associated signalling as well as immunogenicity in a food allergy mouse model.Heating of Ara h 2 led to significantly enhanced binding to Caco-2/TC7 human intestinal epithelial cells. Structural analyses indicated that heating caused persistent structural changes and led to the formation of Ara h 2 oligomers in solution. Heated protein exhibited a significantly higher immunogenic potential in vivo as determined by IgG and IgE serum antibody levels as well as IL-2 and IL-6 release by splenocytes. In human Caco-2/TC7 cells, Ara h 2 incubation led to a response in immune- and stress signalling related pathway components at the RNA level, whereas heated allergen induced a stress-response only.We suggest from this peanut allergen example that food processing may change the molecular immunogenicity and modulate the interaction capacity of food allergens with the intestinal epithelium. Increased binding behaviour to enterocytes and initiation of signalling pathways could trigger the epimmunome and influence the sensitization capacity of food proteins.

先前的研究表明，蛋白质的特定分子特性可能决定了它们的致敏性。过敏原与上皮细胞的相互作用作为第一个接触点可能是决定性的结果免疫反应。我们在这里研究了花生过敏原Ara h2的热处理是否会导致结构变化，从而影响蛋白质与肠细胞的分子相互作用、随后的细胞信号反应和免疫原性。在食物过敏小鼠模型中，对Ara h2进行热处理并分析患者IgE结合、结构改变、与人肠细胞的相互作用、相关信号传导以及免疫原性。加热Ara h2可显著增强其与Caco-2/TC7人肠上皮细胞的结合。结构分析表明，加热引起了持续的结构变化，并导致溶液中Ara h2低聚物的形成。通过血清IgG和IgE抗体水平以及脾细胞释放IL-2和IL-6来测定，加热蛋白在体内表现出明显更高的免疫原性潜力。在人Caco-2/TC7细胞中，Ara h2孵育在RNA水平上导致免疫和应激信号相关途径组分的反应，而加热的过敏原仅诱导应激反应。以花生过敏原为例，我们认为食品加工可能改变了分子免疫原性，并调节了食物过敏原与肠上皮的相互作用能力。增加与肠细胞的结合行为和信号通路的启动可以触发免疫组并影响食物蛋白质的致敏能力。

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引用次数: 34

Anti-idiotypic Fab Fragments Image a Conserved N-terminal Epitope Patch of Grass Pollen Allergen Phl p 1. 草花粉过敏原php1 n端保守表位片段抗独特型Fab片段图像。

The Open Allergy Journal

Pub Date : 2011-05-23 DOI: 10.2174/1874838401104010016

Anna Lukschal, Jan Fuhrmann, Juryj Sobanov, Dirk Neumann, Julia Wallmann, Regina Knittelfelder, Wolfgang Hemmer, Otto Scheiner, Monique Vogel, Beda M Stadler, Erika Jensen-Jarolim, Krisztina Szalai

BACKGROUND AND AIMS: Naturally occurring anti-idiotypic antibodies structurally mimic the original antibody epitope. Anti-idiotypes, therefore, are interesting tools for the portrayal of conformational B-cell epitopes of allergens. In this study we used this strategy particularly for major timothy grass pollen (Phleum pratense) allergen Phl p 1. METHODS AND RESULTS: We used a combinatorial phage display library constructed from the peripheral IgG repertoire of a grass pollen allergic patient which was supposed to contain anti-idiotypic Fab specificities. Using purified anti-Phl p 1 IgG for biopanning, several Fab displaying phage clones could be isolated. 100 amplified colonies were screened for their binding capacity to anti-Phl p 1-specific antibodies, finally resulting in four distinct Fab clones according to sequence analysis. Interestingly, heavy chains of all clones derived from the same germ line sequence and showed high homology in their CDRs. Projecting their sequence information on the surface of the natural allergen Phl p 1 (PDB ID: 1N10) indicated matches on the N-terminal domain of the homo-dimeric allergen, including the bridging region between the two monomers. The resulting epitope patches were formed by spatially distant sections of the primary allergen sequence. CONCLUSION: In this study we report that anti-idiotypic specificities towards anti-Phl p 1 IgG, selected from a Fab library of a grass pollen allergic patient, mimic a conformational epitope patch being distinct from a previously reported IgE epitope area.

背景和目的:自然产生的抗独特型抗体在结构上模仿原始抗体表位。因此，抗独特型是描述过敏原构象b细胞表位的有趣工具。在本研究中，我们特别对主要的蒂莫西草花粉(Phleum pratense)过敏原php1采用了这种策略。方法和结果:我们利用草花粉过敏患者外周血IgG库构建的组合噬菌体展示文库，该文库应该含有抗独特型Fab特异性。用纯化的抗php1 IgG进行生物筛选，可分离出多个Fab噬菌体克隆。筛选100个扩增的菌落对抗php1特异性抗体的结合能力，最终根据序列分析得到4个不同的Fab克隆。有趣的是，所有克隆的重链都来自相同的种系序列，并且在它们的cdr中表现出高度的同源性。将它们的序列信息投射到天然过敏原Phl p 1 (PDB ID: 1N10)表面，表明它们在同型二聚体过敏原的n端结构域上匹配，包括两个单体之间的桥接区域。所得到的表位斑块是由原过敏原序列的空间距离部分形成的。结论:在这项研究中，我们报道了从草花粉过敏患者的Fab文库中选择的抗php1 IgG的抗独特型特异性，模拟了与先前报道的IgE表位区域不同的构象表位斑块。

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引用次数: 0

Pediatric Asthma in Southern Africa 非洲南部儿童哮喘

The Open Allergy Journal

Pub Date : 2011-05-06 DOI: 10.2174/1874838401104010008

R. Green

Pediatric asthma has been well researched and actively managed in Southern Africa for many years. From the earliest study of asthma prevalence in 1979 revealing a significant rural - urban asthma gradient to more recent studies suggesting that asthma now abounds in all population and socio-economic groups, Southern Africa has been the subject of a significant number of publications relating to asthma prevalence, etiologies or associations and treatment guidelines. Asthma is now present in 20% of school-children across Southern Africa, but may not have the same etiological factors commonly seen in the West. Southern Africa has areas with a high asthma prevalence, areas with amongst the highest mortality in the world and similar problems to first-world countries with regard to morbidity and cost of disease. Guide- lines for asthma management published from South Africa highlight the importance of aiming for complete asthma con- trol and avoiding morbidity, exacerbations and mortality.

在非洲南部，儿童哮喘多年来得到了很好的研究和积极的管理。从1979年最早的哮喘患病率研究揭示了显著的农村-城市哮喘梯度，到最近的研究表明哮喘现在在所有人口和社会经济群体中都很普遍，南部非洲一直是大量关于哮喘患病率、病因或关联和治疗指南的出版物的主题。在非洲南部，20%的学龄儿童患有哮喘，但可能与西方常见的病因不同。南部非洲有哮喘高发地区，是世界上死亡率最高的地区之一，在发病率和疾病费用方面与第一世界国家存在类似的问题。南非出版的哮喘管理指南强调了以完全控制哮喘和避免发病、恶化和死亡为目标的重要性。

引用次数: 8

Urticaria as Symptom of Parasite Migration Through the Biological Barriers 荨麻疹是寄生虫通过生物屏障迁移的症状

The Open Allergy Journal

Pub Date : 2011-03-01 DOI: 10.2174/1874838401104010001

A. Bakiri, E. Mingomataj

The absence of a consistent link between parasitoses and urticarial symptoms in the clinical investigations con- trasts to the fact that some parasites are the most potent inducers of immunoglobulin E that exist in nature. To shed some light into this question, this review is focused on the actual knowledge regarding parasites life cycle, interactions with host immunity, the influence on host behavior, and finally the role of all these factors on the urticaria development. The col- lected data demonstrate that parasites could manipulate the host behavior for its own benefit in different ways, inducing urticarial reactions during penetration into different biological barriers. In this context, urticaria may be associated with certain stages of the parasites' life cycle or with host tissue location, but not necessarily only with their presence in the host organism. As compared to T helper (Th) 1, the Th2 response, the eosinophilic infiltration and the complement inhibi- tion could assure a more pleasant surrounding area for the development of some parasites. Taken together, these concepts could explain the epidemiological discrepancy between low rates of urticaria occurrence, and the usual parasites-induced Th2 response. However, further studies are necessary to provide better-based conclusions.

在临床研究中，寄生虫与荨麻疹症状之间缺乏一致的联系，这与某些寄生虫是自然界中存在的免疫球蛋白E最有效的诱导剂这一事实形成了对比。本文就寄生虫的生命周期、与宿主免疫的相互作用、对宿主行为的影响以及这些因素在荨麻疹发病中的作用等方面的研究进展作一综述。收集到的数据表明，寄生虫可以以不同的方式操纵宿主的行为以达到自己的利益，在渗透到不同的生物屏障时诱导荨麻疹反应。在这种情况下，荨麻疹可能与寄生虫生命周期的某些阶段或宿主组织位置有关，但不一定只与它们在宿主有机体中的存在有关。与辅助性T (Th) 1相比，Th2应答、嗜酸性浸润和补体抑制可以为某些寄生虫的发育提供更舒适的环境。综上所述，这些概念可以解释荨麻疹低发生率与通常由寄生虫引起的Th2反应之间的流行病学差异。然而，需要进一步的研究来提供更有根据的结论。

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引用次数: 7

Basophil Activation Antigens: Molecular Mechanisms and Clinical Implications 嗜碱性粒细胞活化抗原:分子机制和临床意义

The Open Allergy Journal

Pub Date : 2010-11-26 DOI: 10.2174/1874838401003010052

P. Valent

Basophil activation is a key finding in allergic reactions and also observed quite frequently in infectious dis- eases and autoimmune disorders. In allergic reactions, basophil-derived mediators such as histamine, contribute essen- tially to clinical symptoms. During IgE-dependent degranulation of basophils, a number of cell surface membrane and cy- toplasmic molecules become activated, show altered expression, or are translocated into the cell surface. Although little is known so far about the exact role of these activation-linked cell surface antigens, several of them are employed as diag- nostic parameters in allergic disorders. Other molecules are involved in the process of signalling and the consecutive re- lease of pro-allergic mediators, and have therefore been proposed as potential targets of therapy. The current article pro- vides a summary on activation-linked cell surface and cytoplasmic antigens in basophils, with special reference to poten- tial mechanisms underlying re-translocation or over-expression in activated cells, relevant signalling pathways, and clini- cal implications. This study was supported by: Fonds zur Forderung der Wissenschaftlichen Forschung in Osterreich, SFB grant # 018-20.

嗜碱性粒细胞活化是过敏反应的关键发现，在感染性疾病和自身免疫性疾病中也经常观察到。在过敏反应中，嗜碱性细胞衍生的介质，如组胺，在很大程度上促成了临床症状。在嗜碱性细胞的ige依赖性脱颗粒过程中，许多细胞膜和细胞质分子被激活，表现出表达改变，或被转移到细胞表面。尽管迄今为止对这些活化相关细胞表面抗原的确切作用知之甚少，但其中一些抗原被用作过敏性疾病的诊断参数。其他分子参与信号传递和促过敏介质的连续释放过程，因此被认为是潜在的治疗靶点。本文综述了嗜碱性细胞中活化相关的细胞表面和细胞质抗原，特别提到了活化细胞中再易位或过表达的潜在机制、相关的信号通路和临床意义。本研究由:奥地利科学研究基金会资助，SFB资助号018-20。

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引用次数: 7

Nonredundant Roles for Basophils in Immediate- and Delayed-onset Allergic Reactions 嗜碱性粒细胞在即发性和迟发性过敏反应中的非冗余作用

The Open Allergy Journal

Pub Date : 2010-11-26 DOI: 10.2174/1874838401003010073

H. Karasuyama, K. Mukai, K. Obata, Y. Tsujimura, Y. Kawano, Y. Minegishi

Basophils circulate in the peripheral blood under physiological conditions, and they are recruited to affected tissues in allergic reactions, albeit in small numbers. Because of their rarity (less than 1% of peripheral blood leukocytes are basophils), and their similarity to mast cells, basophils have often been considered the lesser relatives of mast cells. Moreover, because basophils have been so difficult to identify, mice were erroneously believed for a long time to lack them. Therefore, the assumption that basophils have only redundant roles has remained unquestioned until recently. The flow-cytometric identification of basophils in mice and the development of in vivo models and reagents useful for their functional analyses have greatly advanced the field of basophil research. Previously unrecognized roles of basophils, dis- tinct from those of mast cells, have been shown in allergic responses and the regulation of acquired immunity. In this re- view, we mainly focus on roles of basophils in immediate- and delayed-onset allergic reactions. Basophils are crucial ini- tiators, rather than effectors, in the development of IgE-mediated, chronic cutaneous allergic inflammation, which is char- acterized by the massive infiltration of eosinophils and neutrophils and can be elicited even in the absence of mast cells and T cells. Basophils are dispensable for the induction of IgE-mediated systemic anaphylaxis, unlike mast cells, but play a major role in IgG-mediated passive and active systemic anaphylaxis, through the release of platelet-activating factor in response to stimulation with antigen-IgG immune complexes. Thus, basophils and their products appear to be promising therapeutic targets for allergic disorders.

在生理条件下，嗜碱性粒细胞在外周血中循环，它们在过敏反应中被招募到受影响的组织中，尽管数量很少。由于它们的罕见性(少于1%的外周血白细胞是嗜碱性细胞)，以及它们与肥大细胞的相似性，嗜碱性细胞通常被认为是肥大细胞的次要亲戚。此外，由于嗜碱性粒细胞难以识别，长期以来，人们错误地认为小鼠缺乏它们。因此，嗜碱性细胞只有冗余作用的假设直到最近才受到质疑。流式细胞术对小鼠嗜碱性细胞的鉴定以及对其功能分析的体内模型和试剂的开发，极大地推动了嗜碱性细胞研究领域的发展。以前未被认识到的嗜碱性细胞的作用，不同于肥大细胞的作用，已经显示在过敏反应和获得性免疫的调节中。在这篇综述中，我们主要关注嗜碱性细胞在即发性和迟发性过敏反应中的作用。在ige介导的慢性皮肤过敏性炎症的发展中，嗜碱性粒细胞是至关重要的促动因子，而不是效应因子。慢性皮肤过敏性炎症的特点是嗜酸性粒细胞和中性粒细胞的大量浸润，即使在肥大细胞和T细胞缺乏的情况下也能被诱发。与肥大细胞不同，嗜碱性粒细胞在诱导ige介导的全身性过敏反应中是不可缺少的，但在igg介导的被动和主动全身性过敏反应中发挥主要作用，通过在抗原- igg免疫复合物刺激下释放血小板活化因子。因此，嗜碱性粒细胞及其产物似乎是过敏性疾病的有希望的治疗靶点。

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引用次数: 0

Basophil Functions During Type 2 Inflammation: Initiators, Regulators and Effectors 2型炎症中的嗜碱性细胞功能:启动者、调节者和效应者

The Open Allergy Journal

Pub Date : 2010-11-26 DOI: 10.2174/1874838401003010046

M. Siracusa, D. Artis

Recent studies have identified several previously unrecognized functions of basophils in multiple models of Th2 cytokine-dependent immunity and inflammation. In addition to their established role as effector cells in inflamed tis- sues, findings now indicate that basophils express MHC class II and co-stimulatory molecules, can migrate into draining lymph nodes, present antigen to naive CD4 + T cells and promote Th2 cell differentiation. In this context, basophils have been shown to be critically important for the induction and propagation of Th2 cytokine responses following exposure to helminth parasites and allergens. This article reviews recent conceptual advances in our understanding of basophil biology in the context of allergy and helminth infection.

最近的研究发现了嗜碱性细胞在多种Th2细胞因子依赖性免疫和炎症模型中的一些以前未被认识到的功能。除了在炎症性炎症中作为效应细胞的既定作用外，现在的研究结果表明，嗜碱性细胞表达MHC II类和共刺激分子，可以迁移到引流淋巴结，将抗原呈递给幼稚的CD4 + T细胞并促进Th2细胞分化。在这种情况下，嗜碱性细胞已被证明对暴露于寄生虫和过敏原后Th2细胞因子反应的诱导和繁殖至关重要。本文回顾了在过敏和蠕虫感染的背景下，我们对嗜碱性细胞生物学的理解的最新概念进展。

引用次数: 3