Induction of bystander tolerance and immune deviation after Fel d 1 peptide immunotherapy

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IL-21 promotes allergic airway inflammation by driving apoptosis of FoxP3+ regulatory T cells

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Modulation of eosinophil migration from bone marrow to lungs of allergic rats by nitric oxide

Chronic blockade of nitric oxide (NO) synthesis attenuates the eosinophil infiltration into airways of allergic rats. This study was designed to investigate whether the inhibition of eosinophil influx to the lung of allergic rats reflects modifications in the pattern of cell mobilization from the bone marrow to peripheral blood and/or to lung. Male Wistar rats were treated with N(omega)-nitro-l-arginine methyl ester (l-NAME; 20mg/rat per day) for 4 weeks and sensitized with ovalbumin (OVA). In control rats, the pulmonary OVA-challenge promoted an early (24h) increase in the bone marrow eosinophil population that normalized at 48 h after OVA-challenge, at which time the eosinophils disappeared from the blood and reached the lungs in mass. In l-NAME-treated rats, an accumulation of eosinophils in bone marrow was observed at 24 and 48 h post-OVA-challenge. No variation in this cell type number was observed in peripheral blood and bronchoalveolar lavage throughout the time-course studied. In control rats, the adhesion of bone marrow eosinophils to fibronectin-covered wells was significantly increased at 24h after OVA-challenge, whereas in l-NAME-treated rats the increased adhesion was detected at 48 h. A 32% decrease in the expression of inducible nitric oxide synthase (iNOS) (but not endothelial nitric oxide synthase; eNOS) in eosinophils from l-NAME-treated rats was observed. The levels of IgE, IgG(1) and IgG(2a) were not affected by the l-NAME treatment. Our findings suggest that inhibition of NO synthesis upregulates the binding of eosinophils to extracellular matrix proteins such as fibronectin, producing a delayed efflux of eosinophils from bone marrow to peripheral blood and lungs.     

Ethanol extracts of Saururus chinensis suppress ovalbumin-sensitization airway inflammation

Aim of the study

The aerial part of Saururus chinensis has been used in folk medicine to treat several inflammatory diseases in China and Korea. Previously, our group reported that anti-asthmatic activity of an ethanol extract of Saururus chinensis (ESC) might occur, in part, via the inhibition of prostaglandin D₂ (PGD₂) and leukotriene C₄ (LTC₄) production, and degranulation reaction in vitro, as well as through the down-regulation of interleukin (IL)-4 and eotaxin mRNA expression in an in vivo ovalbumin-sensitization animal model. However, the effects of Saururus chinensis on eicosanoid generation, as well as Th2 cytokines and eotaxin production in an in vivo asthma model, have not been fully investigated. Moreover, it has not been determined whether ESC can ameliorate airway inflammation in vivo. In the present study, we investigated the therapeutic activity of Saururus chinensis on ovalbumin (OVA)-sensitized airway inflammation and its major phytochemical compositions.

Materials and methods

Asthma was induced in BALB/c mice by ovalbumin-sensitization and inhalation. ESC (10-100 mg/kg) or dexamethasone (5 mg/kg), a positive control, was administered 7 times orally every 12 h from one day before the first challenge to 1 h before the second challenge. The recruitment of inflammatory cells and hyperplasia of goblet cells were evaluated by H&E and PAS staining. Levels of Th2 cytokines, eotaxin, PGD₂ and LTC₄ were measured to evaluate the anti-inflammatory activity of ESC in OVA-sensitized mice. Contents of major components were analyzed by HPLC using a reversed-phase C18 column.

Results

ESC (10 mg/kg) suppressed allergic airway inflammation by inhibition of the production of IL-4 (P < 0.001), IL-5 (P < 0.05), IL-13 (P < 0.001), eotaxin (P < 0.001), PGE₂ (P < 0.001), LTC₄ (P < 0.001) in lung extract and IgE level (P < 0.001) in the serum. In addition, ESC (50 mg/kg) reduced the infiltration of inflammatory cells and hyperplasia of goblet cells in the lung tissues. The anti-inflammatory effect of ESC was comparable to that of the positive control drug, dexamethasone. Its major phytochemical composition includes manassantin A, B and sauchinone.

Conclusions

These results suggest that ESC decreased inflammation and mucus secretion in the OVA-induced bronchial asthma model, and its anti-asthmatic activity may occur in part via the inhibition of Th2 cytokines and eotaxin protein expression, as well as through prostaglandin E₂ (PGE₂) and leukotriene C₄ (LTC₄) generation. This effects may be attributed particularly to the presence of manassantin A, B and sauchinone major component evidenced by a HPLC analysis.     

肿瘤相关抗原OVA66在人肿瘤组织中的表达

目的分析肿瘤相关抗原OVA66在人肿瘤组织中的表达特征,探讨其临床应用价值。方法采用免疫组织化学法检测多种组织肿瘤芯片和肿瘤组织标本(包括胃癌、肠癌、肺癌、乳腺癌、膀胱癌、肾癌和卵巢癌)及其相应的非肿瘤组织中OVA66蛋白的表达,分析其表达与组织的良恶性以及肿瘤转移和临床病理特征的关系。结果 OVA66蛋白在胃、肠、卵巢、膀胱和肾的肿瘤组织中的表达显著高于正常组织,在肺和乳腺肿瘤组织中表达较弱。膀胱癌OVA66的表达与膀胱癌的病理分级呈现相关性,肠癌和膀胱癌的淋巴转移组表达阳性率略高于未转移组,但差异无统计学意义。结论 OVA66蛋白在多数肿瘤组织中均呈高表达,在膀胱癌中与肿瘤病理分级相关,提示OVA66有可能成为新的肿瘤标志物应用于多种肿瘤的辅助诊断。     

Eliciting cytotoxic T-lymphocyte responses from synthetic vectors containing one or two epitopes in a C57BL/6 mouse model using peptide-containing biodegradable microspheres and adjuvants

We describe a vaccine delivery mechanism consisting of a synthetic, non-living vector of large d,l poly(lactic-co-glycolic) acid (PLGA) microspheres that carry specific cytotoxic T lymphocyte (CTL) epitopes. We demonstrate in mice that it can be used to elicit substantial interferon gamma ELISPOT responses to more than one specific epitope in the same individual. Our data suggest that a superior adjuvant configuration for the formulation is to place a TLR-9 agonist CpG inside the microsphere and a TLR-4 agonist MPLA in the injectate solution. This finding contrasts with the observations of others. Our approach provides a means to elicit immune responses efficiently to select epitopes, which may be important for an effective vaccine against HIV.     

Homogeneous PLGA-lipid nanoparticle as a promising oral vaccine delivery system for ovalbumin

In this study, a polymeric lipid nanoparticle (NP) (simplified as Lipid NP) was reported as a promising oral vaccine delivery system. The Lipid NPs composed of a hydrophobic polymeric poly(d,l-lactide-co-glycolide) (PLGA) core and a surface coating of lipid monolayer. Membrane emulsification technique was used to obtain uniform-sized Lipid NPs. Ovalbumin (OVA) was used as a model vaccine. Compared with the pure PLGA NPs, the Lipid NPs achieved higher loading capacity (LC) and entrapment efficiency (EE) for the encapsulated OVA. An in vitro oral release profile showed that the OVA-Lipid NPs were with lower initial burst and could protect the loaded OVA from the harsh gastrointestinal (GI) environment for a long time. In addition, a human microfold cell (M-cell) transcytotic assay demonstrated that due to a lipid layer structure on the particle surface, the Lipid NPs showed higher affinity to the M-cells. Since the M-cell in the intestinal epithelium played an important role in particle transportation as well as intimately associated with the underlying immune cells, the OVA-Lipid NPs effectively induced mucosal and humoral immune responses.     

外源性硫化氢对哮喘大鼠肺Muc5ac表达的影响

目的观察卵白蛋白（ovalbumin,OVA）诱导建立的急性支气管哮喘大鼠模型,探讨气体信号分子硫化氢（H2S）在哮喘发病中的作用。方法选取26只健康SD大鼠,按随机数字表法将其分为哮喘组（n=9）、Naris干预组（n=9）和对照组（n=8）。激发后24h解剖大鼠、取肺,观察大鼠支气管周围炎性细胞浸润程度,并进行评分。采用免疫组化染色法测定外源性硫氢化钠（NaHS）、硫化氢为供体处理后的大鼠肺部黏蛋白基因Muc5ac的表达情况。结果光镜下支气管周围炎性细胞浸润程度评分（中位数表示）,哮喘组为4分,NaHS组为2分,对照组为1分,三组间比较,差异有显著意义（H=13．75,P〈0．05）。哮喘组、NaHS干预组及对照组肺muc5ac蛋白含量（阳性面积表示）分别为（1330．22士662．87）μm^2,（715．88±282．49）μm^2及（501．75±270．58）μm^2,三组间比较,差异有显著意义（F=11．82,P〈O．01）。结论哮喘组大鼠黏蛋白基因Muc5ac表达增加,外源性硫化氢可减轻哮喘气管炎症,对哮喘急性发作起保护作用。