RESUMO
Tricin, a flavone present in rice bran, is confirmed as the major efficacious compound present in the enzyme-treated Zizania latifolia extract (ETZL), which protects against UVB-induced skin-aging. However, the suppressive mechanism of tricin on allergic responses remains unknown. The present study, therefore, aimed to determine the mechanisms of tricin and ETZL on mast cell degranulation in IgE-activated rat basophilic leukemia cell line (RBL-2H3) cells. We investigated the regulatory effects of tricin and ETZL on degranulation, production of cytokines and lipid mediators, and signaling proteins involved in the IgE-bound high-affinity IgE receptor activation, mitogen-activated protein kinase, arachidonic acid and Syk. The production of ß-hexosaminidase, tumor necrosis factor-α, interleukin-4, leukotrienes (LT) B4, LTC4 and prostaglandin E2 in IgE-stimulated RBL-2H3 cells were significantly inhibited by exposure to tricin or ETZL. Moreover, tricin and ETZL inhibit the phosphorylation of cytosolic phospholipase A2, 5-lipoxygenase and cyclooxygenase-2. Furthermore, the phosphorylation of Akt, ERK, p38, JNK, protein kinase Cδ and phospholipase Cγ1 were effectively suppressed by both samples. Exposure to tricin or ETZL also significantly decreases the phosphorylation of Lyn and Syk, but has minimal effect on Fyn. Taken together, our data indicate that tricin and ETZL are potential anti-allergic materials that could be applied for the prevention of allergy-related diseases.
Assuntos
Antialérgicos/farmacologia , Flavonoides/farmacologia , Hipersensibilidade Imediata/imunologia , Hipersensibilidade Imediata/metabolismo , Extratos Vegetais/farmacologia , Poaceae/química , Transdução de Sinais/efeitos dos fármacos , Animais , Antialérgicos/química , Degranulação Celular/efeitos dos fármacos , Linhagem Celular , Citocinas/metabolismo , Células Alimentadoras , Flavonoides/química , Flavonoides/isolamento & purificação , Hipersensibilidade Imediata/tratamento farmacológico , Imunoglobulina E/metabolismo , Mediadores da Inflamação/metabolismo , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Mastócitos/metabolismo , Estrutura Molecular , Extratos Vegetais/química , Ratos , Receptores de IgE/metabolismoRESUMO
BACKGROUND: Allergen exposure and air pollution are two risk factors for asthma development and airway inflammation that have been examined extensively in isolation. The impact of combined allergen and diesel exhaust exposure has received considerably less attention. Diesel exhaust (DE) is a major contributor to ambient particulate matter (PM) air pollution, which can act as an adjuvant to immune responses and augment allergic inflammation. We aimed to clarify whether DE increases allergen-induced inflammation and cellular immune response in the airways of atopic human subjects. METHODS: Twelve atopic subjects were exposed to DE 300 µg.m(-3) or filtered air for 2 h in a blinded crossover study design with a four-week washout period between arms. One hour following either filtered air or DE exposure, subjects were exposed to allergen or saline (vehicle control) via segmental challenge. Forty-eight hours post-allergen or control exposure, bronchial biopsies were collected. The study design generated 4 different conditions: filtered air + saline (FAS), DE + saline (DES), filtered air + allergen (FAA) and DE + allergen (DEA). Biopsies sections were immunostained for tryptase, eosinophil cationic protein (ECP), neutrophil elastase (NE), CD138, CD4 and interleukin (IL)-4. The percent positivity of positive cells were quantified in the bronchial submucosa. RESULTS: The percent positivity for tryptase expression and ECP expression remained unchanged in the bronchial submucosa in all conditions. CD4 % positive staining in DEA (0.311 ± 0.060) was elevated relative to FAS (0.087 ± 0.018; p = 0.035). IL-4% positive staining in DEA (0.548 ± 0.143) was elevated relative to FAS (0.127 ± 0.062; p = 0.034). CD138 % positive staining in DEA (0.120 ± 0.031) was elevated relative to FAS (0.017 ± 0.006; p = 0.015), DES (0.044 ± 0.024; p = 0.040), and FAA (0.044 ± 0.008; p = 0.037). CD138% positive staining in FAA (0.044 ± 0.008) was elevated relative to FAS (0.017 ± 0.006; p = 0.049). NE percent positive staining in DEA (0.224 ± 0.047) was elevated relative to FAS (0.045 ± 0.014; p = 0.031). CONCLUSIONS: In vivo allergen and DE co-exposure results in elevated CD4, IL-4, CD138 and NE in the respiratory submucosa of atopic subjects, while eosinophils and mast cells are not changed. TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01792232.
Assuntos
Poluentes Atmosféricos/efeitos adversos , Alérgenos , Brônquios/efeitos dos fármacos , Hipersensibilidade Imediata/imunologia , Material Particulado/efeitos adversos , Pneumonia/imunologia , Hipersensibilidade Respiratória/imunologia , Emissões de Veículos , Adulto , Poluentes Atmosféricos/imunologia , Animais , Betula/imunologia , Biomarcadores/metabolismo , Biópsia , Brônquios/imunologia , Brônquios/metabolismo , Brônquios/patologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Hipersensibilidade Imediata/diagnóstico , Hipersensibilidade Imediata/metabolismo , Imuno-Histoquímica , Mediadores da Inflamação/metabolismo , Interleucina-4/metabolismo , Elastase de Leucócito/metabolismo , Masculino , Pessoa de Meia-Idade , Material Particulado/imunologia , Pneumonia/induzido quimicamente , Pneumonia/diagnóstico , Pneumonia/metabolismo , Poaceae/imunologia , Pólen/imunologia , Pyroglyphidae/imunologia , Hipersensibilidade Respiratória/diagnóstico , Hipersensibilidade Respiratória/metabolismo , Sindecana-1/metabolismo , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: Late allergic reactions are common in the course of allergen-specific immunotherapy and even occur with allergy vaccines with reduced IgE reactivity. OBJECTIVE: We sought to study atopy patch test (APT) reactions and T-cell responses to the recombinant birch pollen allergen Bet v 1 and recombinant hypoallergenic T-cell epitope-containing Bet v 1 fragments in patients with birch pollen allergy with and without atopic dermatitis (AD). METHODS: A clinical study was conducted in 15 patients with birch pollen allergy with AD (group 1), 5 patients with birch pollen allergy without AD (group 2), 5 allergic patients without birch pollen allergy (group 3), and 5 nonallergic subjects (group 4) by performing skin prick tests and APTs with rBet v 1 and hypoallergenic rBet v 1 fragments. T-cell, cutaneous lymphocyte antigen (CLA)(+) and CCR4(+) T-cell and cytokine responses were studied by thymidine uptake, carboxyfluorescein diacetate succinimidyl ester staining, and Luminex technology, respectively. RESULTS: rBet v 1 and hypoallergenic rBet v 1 fragments induced APT reactions in not only most of the patients with birch pollen allergy with AD (11/15) but also in most of those without AD (4/5). Patients with birch pollen allergy with AD had higher Bet v 1-specific proliferation of CLA(+) and CCR4(+) T cells compared with patients with birch pollen allergy without AD. There were no differences in Bet v 1-specific CLA(+) and CCR4(+) proliferation and cytokine secretion in patients with and without APT reactions. CONCLUSION: Hypoallergenic rBet v 1 fragments induce T cell-dependent late reactions not only in patients with birch pollen allergy with AD but also in those without AD, which can be determined based on APT results but not based on in vitro parameters.
Assuntos
Alérgenos/imunologia , Antígenos de Plantas/imunologia , Hipersensibilidade Tardia/diagnóstico , Hipersensibilidade Tardia/imunologia , Testes do Emplastro , Linfócitos T/imunologia , Adulto , Betula/efeitos adversos , Citocinas/biossíntese , Dermatite Atópica/diagnóstico , Dermatite Atópica/imunologia , Dermatite Atópica/metabolismo , Feminino , Liberação de Histamina , Humanos , Hipersensibilidade Tardia/metabolismo , Hipersensibilidade Imediata/diagnóstico , Hipersensibilidade Imediata/imunologia , Hipersensibilidade Imediata/metabolismo , Ativação Linfocitária/imunologia , Masculino , Pólen/imunologia , Rinite Alérgica Sazonal/diagnóstico , Rinite Alérgica Sazonal/imunologia , Especificidade do Receptor de Antígeno de Linfócitos T/imunologia , Linfócitos T/metabolismo , Adulto JovemRESUMO
BACKGROUND: Respiratory allergy triggered by pollen allergens is increasing at an alarming rate worldwide. Sunflower pollen is thought to be an important source of inhalant allergens. Present study aims to identify the prevalence of sunflower pollinosis among the Indian allergic population and characterizes the pollen allergens using immuno-proteomic tools. METHODOLOGY: Clinico-immunological tests were performed to understand the prevalence of sensitivity towards sunflower pollen among the atopic population. Sera from selected sunflower positive patients were used as probe to detect the IgE-reactive proteins from the one and two dimensional electrophoretic separated proteome of sunflower pollen. The antigenic nature of the sugar moiety of the glycoallergens was studied by meta-periodate modification of IgE-immunoblot. Finally, these allergens were identified by mass-spectrometry. RESULTS: Prevalence of sunflower pollen sensitization was observed among 21% of the pollen allergic population and associated with elevated level of specific IgE and histamine in the sera of these patients. Immunoscreening of sunflower pollen proteome with patient sera detected seven IgE-reactive proteins with varying molecular weight and pI. Hierarchical clustering of 2D-immunoblot data highlighted three allergens characterized by a more frequent immuno-reactivity and increased levels of IgE antibodies in the sera of susceptible patients. These allergens were considered as the major allergens of sunflower pollen and were found to have their glycan moiety critical for inducing IgE response. Homology driven search of MS/MS data of these IgE-reactive proteins identified seven previously unreported allergens from sunflower pollen. Three major allergenic proteins were identified as two pectate lyases and a cysteine protease. CONCLUSION: Novelty of the present report is the identification of a panel of seven sunflower pollen allergens for the first time at immuno-biochemical and proteomic level, which substantiated the clinical evidence of sunflower allergy. Further purification and recombinant expression of these allergens will improve component-resolved diagnosis and therapy of pollen allergy.
Assuntos
Alérgenos/imunologia , Antígenos de Plantas/imunologia , Helianthus/imunologia , Proteínas de Plantas/imunologia , Pólen/imunologia , Proteoma/análise , Proteômica/métodos , Adolescente , Adulto , Alérgenos/metabolismo , Antígenos de Plantas/metabolismo , Estudos de Casos e Controles , Eletroforese em Gel Bidimensional , Feminino , Helianthus/metabolismo , Humanos , Hipersensibilidade Imediata/diagnóstico , Hipersensibilidade Imediata/imunologia , Hipersensibilidade Imediata/metabolismo , Immunoblotting , Imunoglobulina E/imunologia , Imunoglobulina E/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas de Plantas/metabolismo , Pólen/metabolismo , Sistema Respiratório/imunologia , Sistema Respiratório/metabolismo , Rinite Alérgica Sazonal/diagnóstico , Rinite Alérgica Sazonal/imunologia , Pele/imunologia , Pele/metabolismo , Espectrometria de Massas em Tandem , Adulto JovemRESUMO
Dendritic cells (DCs) are sentinels of the immune system for antigen recognition and uptake, as well as presentation to naïve T cells for stimulation or priming. Internalization and endocytic degradation of allergens by DCs are important steps required for T cell priming. In the current study we investigated binding and internalization of purified recombinant non-glycosylated grass pollen allergen, Phl p 5, and natural non-specific lipid transfer protein from sunflower, SF-nsLTP to human monocyte derived dendritic cells (MoDCs). Colocalization of Phl p 5 with low affinity (CD23) or high affinity receptor (FcεRI) was investigated by immunofluorescence staining. Likewise, localization of the allergens in early (EE) and late endosomes (LE) was detected by co-staining for early endosome antigen (EEA1) and lysosomal-associated membrane protein 1 (LAMP1). In our experimental setting we could demonstrate that Phl p 5 as well as SF-nsLTP bound to MoDCs from both, grass pollen allergic and non-allergic individuals. Competitive allergen uptake experiments demonstrated non-preferential and simultaneous uptake of Phl p 5 and SF-nsLTP by MoDCs. No overlap of signals from Phl p 5 and CD23 or FcεRI was detectable, excluding IgE-mediated uptake for this allergen. Both allergens, Phl p 5 and SF-nsLTP, were localized in early and late endosomes. The present study applied a set of methods to assess the allergen uptake by MoDCs in an in vitro model. No qualitative and quantitative differences in the allergen uptake of both, Phl p 5 and SF-nsLTP were detected in single and competitive assays.
Assuntos
Alérgenos/imunologia , Células Dendríticas/imunologia , Hipersensibilidade Imediata/imunologia , Proteínas de Plantas/imunologia , Pólen/imunologia , Adulto , Alérgenos/metabolismo , Transporte Biológico , Células Dendríticas/metabolismo , Endossomos/metabolismo , Feminino , Humanos , Hipersensibilidade Imediata/diagnóstico , Hipersensibilidade Imediata/metabolismo , Imunoglobulina E/imunologia , Imunoglobulina E/metabolismo , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Proteínas de Plantas/metabolismo , Ligação Proteica , Receptores de IgE/metabolismo , Rinite Alérgica Sazonal/diagnóstico , Rinite Alérgica Sazonal/imunologia , Rinite Alérgica Sazonal/metabolismo , Adulto JovemRESUMO
The purpose of this study was to summarize and analyze the results of studies supporting the use of omega-3 fatty acids for their therapeutic and preventive value in childhood asthma in light of recent genetic evidence strongly suggesting a pathogenetic role in asthma and to discuss the implications of these findings for future research. Although a considerable number of observational studies have been conducted in children showing a beneficial effect of omega-3 dietary intake in asthma, a fully well-designed, rigorously conducted investigational study is still lacking. Additionally, the few interventional trials with omega-3 supplementation conducted in asthmatic children have often yielded conflicting results. The genetic polymorphism and the gene-nutritional interactions that accompany asthma can be the missing factors and may explain the inconsistent results found in these interventional trials. Therefore, the analyses of key genes variants should be included in future studies to thoroughly investigate the effects of long-chain polyunsaturated fatty acid on asthma. Although a definitive conclusion can not be made supporting a beneficial effect of dietary modification or supplementation with omega-3 for the prevention or modification of asthmatic disease in children, there is sufficient evidence to support this possibility. There is, therefore, a clear need for future research to investigate the feasibility of this dietetic approach to reduce the likely development of asthma and/or the successful treatment of asthmatic disease. From a public health perspective, if a dietetic approach is successfully documented, even if only in a cohort of susceptible individuals, it would offer a far better management tool than currently available, better tolerated, and, in the long run, more cost-effective.
Assuntos
Asma/etiologia , Dieta , Suplementos Nutricionais , Ácidos Graxos Ômega-3/metabolismo , Asma/metabolismo , Asma/prevenção & controle , Asma/terapia , Criança , Pré-Escolar , Ácidos Graxos Ômega-3/química , Humanos , Hipersensibilidade Imediata/etiologia , Hipersensibilidade Imediata/metabolismo , Lactente , Recém-Nascido , Inflamação/etiologia , Inflamação/metabolismoRESUMO
Nasal allergen challenge can be used to assess the clinical and immunological aspects of rhinitis due to inhalant allergens. We aimed to develop a reproducible technique for grass pollen nasal allergen challenge and to study biomarkers within nasal secretions. 20 Grass pollen allergic individuals underwent nasal challenges with purified Timothy grass allergen. An initial dose-titration challenge was used to determine dose-response characteristics. Subsequently, volunteers underwent 3 further challenges using individualised threshold doses. Symptom scores, visual analogue scores, and peak nasal inspiratory flow (PNIF) were recorded at baseline and up to 6h after challenge. Nasal secretions were collected at each time point using synthetic filter papers or absorptive polyurethane sponges and analysed for IL-4, -5, -10, -13, IFN-γ, Tryptase and Eosinophil Cationic Protein (ECP). Challenges gave reproducible symptom scores and decreased PNIF. Tryptase levels in nasal fluid peaked at 5 min after challenge and returned to baseline levels at 1h. ECP, IL-5, IL-13 and IL-4 levels were increased from 2-3 h and showed progressive increases to 5-6 h. Sponges proved the superior nasal fluid sampling technique. We have developed a reproducible nasal allergen challenge technique. This may be used as a surrogate clinical endpoint in trials assessing the efficacy of treatments for allergic rhinitis. Tryptase in local nasal secretions is a potential biomarker of the early phase response; ECP and the Th2 cytokines IL-5, -13 and -4 markers of late phase allergic responses. Our model allows correlation between clinical responses and local biomarkers following nasal allergen challenge.
Assuntos
Alérgenos/imunologia , Hipersensibilidade Imediata/imunologia , Testes de Provocação Nasal/métodos , Pólen/imunologia , Rinite Alérgica Sazonal/imunologia , Adulto , Alérgenos/metabolismo , Proteína Catiônica de Eosinófilo/imunologia , Proteína Catiônica de Eosinófilo/metabolismo , Feminino , Humanos , Hipersensibilidade Imediata/diagnóstico , Hipersensibilidade Imediata/metabolismo , Interferon gama/imunologia , Interferon gama/metabolismo , Interleucina-10/imunologia , Interleucina-10/metabolismo , Interleucina-13/imunologia , Interleucina-13/metabolismo , Interleucina-4/imunologia , Interleucina-4/metabolismo , Interleucina-5/imunologia , Interleucina-5/metabolismo , Masculino , Pessoa de Meia-Idade , Phleum/imunologia , Phleum/metabolismo , Pólen/metabolismo , Reprodutibilidade dos Testes , Rinite Alérgica Sazonal/diagnóstico , Rinite Alérgica Sazonal/metabolismo , Sensibilidade e Especificidade , Fatores de Tempo , Triptases/imunologia , Triptases/metabolismo , Adulto JovemRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: KOB03 is a polyherbal medicine consisting of five different herbs and has commonly been used for the treatment of various allergic diseases. However, its precise anti-allergic effect and mechanism remain unknown. AIM OF THE STUDY: The aim of this study was to investigate the effect of KOB03 on allergic responses through the regulation of mast-cell mediated allergic inflammation. MATERIALS AND METHODS: To determine the effect of KOB03 on mast cell-mediated allergic reactions, we investigated the parameter changes of in vivo models such as compound 48/80-induced systemic anaphylaxis and ovalbumin (OVA)-induced allergic rhinitis, and the release of allergic inflammatory mediators such as histamine, immunoglobulin (Ig) E, and inflammatory cytokines via the MAPKs and NF-kappaB pathways. RESULTS: The oral administration of KOB03 at doses of 100 and 200mg/kg inhibited histamine release and mortality in compound 48/80-induced anaphylactic rats. KOB03 also improved rhinitis symptoms, inhibited the histopathological changes of nasal mucosa, and decreased the serum levels of histamine, OVA-specific IgE and TNF-α in OVA-induced allergic rhinitis in mice. In vitro, KOB03 suppressed compound 48/80-induced histamine release by blocking mast cell degranulation. In addition, KOB03 inhibited the production of inflammatory cytokines such as TNF-α, IL-1ß, IL-6 and IL-8 in PMA/A23187-stimulated HMC-1 mast cells by suppressing their gene expression and blocking the ERK1/2 and p38 MAPK and NF-κB pathways. CONCLUSIONS: These results suggest that KOB03 has an anti-allergic effect by modulating mast cell-mediated allergic responses in allergic rhinitis.
Assuntos
Antialérgicos/uso terapêutico , Hipersensibilidade Imediata/tratamento farmacológico , Magnoliopsida , Fitoterapia , Extratos Vegetais/uso terapêutico , Preparações de Plantas/uso terapêutico , Rinite/tratamento farmacológico , Alérgenos , Animais , Antialérgicos/farmacologia , Linhagem Celular , Citocinas/sangue , Citocinas/genética , Liberação de Histamina/efeitos dos fármacos , Humanos , Hipersensibilidade Imediata/induzido quimicamente , Hipersensibilidade Imediata/metabolismo , Imunoglobulina E/sangue , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Cavidade Nasal , Ovalbumina , Extratos Vegetais/farmacologia , Preparações de Plantas/farmacologia , RNA Mensageiro/metabolismo , Rinite/induzido quimicamente , Rinite/metabolismo , p-Metoxi-N-metilfenetilaminaRESUMO
BACKGROUND: Several studies in mice have recently shown that basophils can act as antigen-presenting cells (APC) inducing Th2-mediated immune responses against parasites or protease allergens. The aim of this study was to investigate whether human basophils function as APC for the major birch pollen allergen Bet v 1. METHODS: Fluorescently labeled Bet v 1 was used to assess surface binding and internalization of allergen by basophils and different types of APC from birch pollen-allergic and nonallergic individuals. Sorted basophils were analyzed in terms of up-regulation of MHC class II and co-stimulatory molecules in the absence and presence of IL-3 and IFN-γ by flow cytometry. Expression of proteins crucial for antigen presentation, namely cathepsin S and invariant chain, was determined. Basophils were used as APC in co-culture experiments with Bet v 1-specific T-cell clones (TCCs). RESULTS: Basophils from birch pollen-allergic donors very efficiently bound Bet v 1 through IgE/FcεRI complexes on their surface. In contrast to professional APC, basophils did not internalize allergen and expressed marginal levels of cathepsin S and invariant chain. HLA-DP, HLA-DQ, CD80/CD86, and CD40 were absent from purified basophils even when stimulated with IL-3 plus IFN-γ. IL-3/IFN-γ marginally up-regulated HLA-DR. Bet v 1-pulsed basophils failed to induce proliferative and cytokine responses in Bet v 1-specific, HLA-DR-restricted TCCs. CONCLUSION: Human basophils neither internalize, process nor present Bet v 1. Because Bet v 1 is a highly relevant allergen, we conclude that basophils play no role as APC in IgE-mediated allergy in humans.
Assuntos
Alérgenos/imunologia , Células Apresentadoras de Antígenos/imunologia , Antígenos de Plantas/imunologia , Basófilos/imunologia , Pólen/imunologia , Antígenos de Plantas/metabolismo , Basófilos/metabolismo , Endocitose/imunologia , Epitopos/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Hipersensibilidade Imediata/imunologia , Hipersensibilidade Imediata/metabolismo , Ligação Proteica/imunologia , Receptores de IgE/imunologia , Receptores de IgE/metabolismo , Linfócitos T/imunologiaRESUMO
BACKGROUND: Basophil activation tests (BAT) rely on different combinations of basophil selection and activation markers. Whereas activation markers, especially CD63, are widely validated, the most suitable and robust marker for basophil selection is still a matter of debate. AIMS: Comparison of cell surface expression of two commonly used basophil selection markers (IgE, CD123/HLA-DR) with CCR3 in an unselected group of atopic and nonatopic donors in resting and activated basophils. METHODS: EDTA blood of 94 healthy adults, about half of them atopic by history, was analyzed using two different staining strategies: anti-CD123-PE/anti-HLA-DR-PerCP/anti-lin1-FITC and anti-IgE-FITC/anti-CD3-PerCP/anti-CCR3-PE. Additionally 40 pollen-allergic patients were recruited for the assessment of CCR3 expression after basophil activation. RESULTS: In resting basophils, cell surface expression of the three basophil selection markers was most constant for CCR3. IgE gating strategy showed the highest variation and up to 80% of nonbasophils in the selected gate in certain donors. During basophil activation, a shift of the mean fluorescence intensity for CCR3 toward the lower third of the CCR3-positive population could be demonstrated, but neither were CCR3-positive cells significantly lost for further analysis nor was differentiation between CCR3-positive and CCR3-negative cell populations hampered by this shift. CONCLUSIONS: CCR3 is a stable and highly expressed basophil selection marker, independent of the atopic background or basophil activation state and allows an accurate identification of basophils without need of a second marker. The basophil markers CD123/HLA-DR and IgE showed significantly higher interindividual variability in cell surface expression and are therefore less suited as selection markers.
Assuntos
Basófilos/imunologia , Biomarcadores/metabolismo , Citometria de Fluxo/métodos , Receptores CCR3/metabolismo , Adolescente , Adulto , Idoso , Teste de Degranulação de Basófilos/métodos , Basófilos/metabolismo , Feminino , Humanos , Hipersensibilidade Imediata/etiologia , Hipersensibilidade Imediata/imunologia , Hipersensibilidade Imediata/metabolismo , Masculino , Pessoa de Meia-Idade , Pólen/efeitos adversos , Pólen/imunologia , Adulto JovemRESUMO
Although an immunomodulatory role of the soy isoflavone genistein has been demonstrated, the effects of other soy isoflavones on induction of antigen (Ag)-specific immune responses are not known. In this study, we therefore investigated the effects of daidzein and equol on ovalbumin (OVA)-specific T cell and B cell responses in BALB/c mice. Mice that had been treated with 20 mg/kg equol showed a significantly higher level of OVA-specific IgE than control mice. Levels of interferon (IFN)-gamma and interleukin (IL)-4 production were not different between the control and equol groups. However, IL-13 production level in mice administered 20 mg/kg equol was significantly higher than that in control mice. Strong induction of OVA-specific IgE production by equol was also observed in ovariectomized BALB/c mice, suggesting that the immunomodulatory effect of equol is not affected by endogenous estrogen.
Assuntos
Linfócitos B/metabolismo , Glycine max/química , Imunoglobulina E/biossíntese , Fatores Imunológicos/farmacologia , Isoflavonas/farmacologia , Fitoestrógenos/farmacologia , Linfócitos T/metabolismo , Animais , Equol , Estrogênios/fisiologia , Feminino , Hipersensibilidade Imediata/metabolismo , Imunização , Interleucina-13/biossíntese , Isoflavonas/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , OvariectomiaRESUMO
INTRODUCTION: Receptive music therapy (rMT) not only provides a good feeling but also a more effective healing process and mastery of stress. METHODS AND RESULTS: In a preliminary study it could be shown that American Doudouk-music (feel-good music) suppressed salivary histamine secretion in two groups (n = 4) of allergic and non-allergic young volunteers. Stress was induced by eating adverse food/allergenic food during music exposure. There was no response in the vein blood samples and no significant difference between the allergic and non-allergic groups. CONCLUSION: It can be concluded that saliva is an appropriate medium for histamine measurements during music exposure.
Assuntos
Histamina/metabolismo , Musicoterapia , Saliva/metabolismo , Adulto , Cromatografia Líquida de Alta Pressão , Ensaio de Imunoadsorção Enzimática , Feminino , Fluorometria , Histamina/sangue , Humanos , Hipersensibilidade/metabolismo , Hipersensibilidade/terapia , Hipersensibilidade Imediata/metabolismo , Hipersensibilidade Imediata/terapia , Adulto JovemRESUMO
Leukotriene B(4) (LTB(4)) is a lipid mediator with potent chemoattractant properties and that is rapidly generated from activated innate immune cells such as neutrophils, macrophages, and mast cells. Elevated levels of LTB(4) have been reported in various allergic diseases and these levels have been related to disease activity and response to treatment. Recent studies using LTB(4) receptor-1 (BLT1) antagonists or BLT1-deficient mice have revealed that ligation of BLT1 by LTB(4) is important for the activation and recruitment of inflammatory cells including neutrophils, eosinophils, monocytes/macrophages, mast cells, dendritic cells, and more recently, effector T cells to inflamed tissues in various inflammatory diseases. The LTB(4)/BLT1 pathway appears to play an important role in the pathogenesis of severe persistent asthma, aspirin- and exercise-induced asthma, allergic rhinitis, and atopic dermatitis together with other mediators including cysteinyl leukotrienes, cytokines, and chemokines. LTB(4) production is in general resistant to corticosteroid treatment. In fact, corticosteroids can upregulate BLT1 expression on corticosteroid-resistant inflammatory cells such as neutrophils, monocytes, and effector memory CD8+ T cells. As a result, this corticosteroid-resistant LTB(4)/BLT1 pathway may contribute to the development of inflammation in allergic diseases that do not respond to the introduction of corticosteroids. Inhibition of this pathway has potential therapeutic benefit in various allergic diseases that have involvement of corticosteroid-insensitivity.
Assuntos
Linfócitos T CD8-Positivos/metabolismo , Hipersensibilidade Imediata/imunologia , Leucotrieno B4/metabolismo , Receptores do Leucotrieno B4/metabolismo , Células Th2/metabolismo , Corticosteroides/uso terapêutico , Animais , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Movimento Celular/genética , Movimento Celular/imunologia , Citocinas/metabolismo , Suplementos Nutricionais , Ácidos Graxos/uso terapêutico , Óleos de Peixe/uso terapêutico , Humanos , Hipersensibilidade Imediata/metabolismo , Hipersensibilidade Imediata/patologia , Hipersensibilidade Imediata/terapia , Imunidade Inata , Memória Imunológica , Leucotrieno B4/genética , Leucotrieno B4/imunologia , Camundongos , Camundongos Knockout , Receptores do Leucotrieno B4/genética , Receptores do Leucotrieno B4/imunologia , Transdução de Sinais , Células Th2/imunologia , Células Th2/patologiaRESUMO
Summary There is a hypothesis causally linking excess intake of n-6 polyunsaturated fatty acids (PUFAs) to atopic disease. Under most dietary conditions, the main precursor of eicosanoids is the n-6 PUFA arachidonic acid (AA). AA-derived eicosanoids play many roles in sensitization to allergens and in allergic inflammation. Long chain n-3 PUFAs inhibit AA incorporation into cell membranes and inhibit AA metabolism to eicosanoids. It is hypothesized that atopy is associated with a higher n-6 PUFA status and with a low n-3 PUFA status. However, measurements of fatty acid composition do not provide a clear picture that such fatty acid abnormalities exist in atopy with no really clear pattern of altered status of a particular fatty acid or a particular fatty acid family. There are few reports of elevated linoleic acid in atopy. Some studies report lower amounts of the n-6 PUFAs, including AA, and of long chain n-3 PUFAs in atopy, although observations on this are not consistent. Taken together these data clearly do not support the hypothesis that atopy is somehow associated with a high exposure to, and status of, n-6 PUFAs. Intervention studies with n-3 PUFAs in pregnant women, infants and children suggest some clinical benefits, although how long lasting these are remains to be determined. The observation that there may be low AA status in atopy suggests that fish oil intervention, which targets AA status and metabolism, may not be ideal and that a combination of fish oil with some longer chain n-6 PUFAs may be more efficacious.
Assuntos
Gorduras Insaturadas na Dieta/efeitos adversos , Ácidos Graxos Insaturados/química , Hipersensibilidade Imediata/metabolismo , Ácido Araquidônico/biossíntese , Criança , Pré-Escolar , Eicosanoides/biossíntese , Eicosanoides/química , Ácidos Graxos Ômega-3/química , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-6/química , Ácidos Graxos Ômega-6/metabolismo , Ácidos Graxos Insaturados/metabolismo , Feminino , Sangue Fetal/química , Humanos , Hipersensibilidade Imediata/epidemiologia , Hipersensibilidade Imediata/etiologia , Lactente , Recém-Nascido , Leite Humano/químicaRESUMO
The high affinity IgE receptor, Fc epsilonRI, plays a key role in the immunological pathways involved in allergic asthma. Previously we have demonstrated that human neutrophils isolated from allergic asthmatics express a functional Fc epsilonRI, and therefore it was of importance to examine the factors regulating its expression. In this study, we found that neutrophils from allergic asthmatics showed increased expression of Fc epsilonRI-alpha chain surface protein, total protein and mRNA compared with those from allergic non asthmatics and healthy donors (p<0.001). Interestingly, in neutrophils isolated from allergic asthmatics, Fc epsilonRI-alpha chain surface protein and mRNA expression were significantly greater during the pollen season than outside the pollen season (n = 9, P = 0.001), an effect which was not observed either in the allergic non asthmatic group or the healthy donors (p>0.05). Allergen exposure did not affect other surface markers of neutrophils such as CD16/Fc gammaRIII or IL-17R. In contrast to stimulation with IgE, neutrophils incubated with TH2 cytokines IL-9, GM-CSF, and IL-4, showed enhanced Fc epsilonRI-alpha chain surface expression. In conclusion, these results suggest that enhanced Fc epsilonRI expression in human neutrophils from allergic asthmatics during the pollen season can make them more susceptible to the biological effects of IgE, providing a possible new mechanism by which neutrophils contribute to allergic asthma.
Assuntos
Alérgenos/metabolismo , Regulação da Expressão Gênica , Neutrófilos/metabolismo , Receptores de IgE/biossíntese , Células Th2/citologia , Adolescente , Adulto , Asma/sangue , Asma/metabolismo , Humanos , Hipersensibilidade Imediata/sangue , Hipersensibilidade Imediata/metabolismo , Hibridização in Situ Fluorescente , Microscopia de Fluorescência , Pessoa de Meia-Idade , Modelos Biológicos , PólenRESUMO
The classical allergic reaction starts seconds or minutes after Ag contact and is committed by Abs produced by a special subset of B lymphocytes. These Abs belong to the IgE subclass and are responsible for Type I hyperreactivity reactions. Treatment of allergic diseases with humanized anti-IgE Abs leads primarily to a decrease of serum IgE levels. As a consequence, the number of high-affinity IgE receptors on mast cells and basophils decreases, leading to a lower excitability of the effector cells. The biological mechanism behind anti-IgE therapy remains partly speculative; however, it is likely that these Abs also interact with membrane IgE (mIgE) on B cells and possibly interfere with IgE production. In the present work, we raised a mouse mAb directed exclusively against the extracellular membrane-proximal domain of mIgE. The interaction between the monoclonal anti-mIgE Ab and mIgE induces receptor-mediated apoptosis in vitro. Passive immunization experiments lead to a block of newly synthesized specific IgEs during a parallel application of recombinant Bet v1a, the major birch pollen allergen. The decrease of allergen-specific serum IgE might be related to tolerance-inducing mechanisms stopping mIgE-displaying B cells in their proliferation and differentiation.
Assuntos
Alérgenos/imunologia , Linfócitos B/imunologia , Basófilos/imunologia , Hipersensibilidade Imediata/imunologia , Imunização Passiva , Imunoglobulina E/biossíntese , Animais , Anticorpos Monoclonais/imunologia , Especificidade de Anticorpos , Apoptose , Linfócitos B/citologia , Betula/imunologia , Feminino , Hipersensibilidade Imediata/metabolismo , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Pólen/imunologia , Ratos , Receptores de IgE/metabolismoRESUMO
Ixeris dentata (ID, family Asteraceae), called Seumbakuy in Korea, was fermented with lactic acid bacteria (LAB) and their antiallergic activities were investigated. Fermentation of ID with Bifidobacterium breve or Lactobacillus acidophilus increased its inhibition of degranulation in RBL-2H3 cells induced by the IgE-antigen complex. Oral administration of these extracts to mice inhibited the passive cutaneous anaphylaxis (PCA) reaction induced by the IgE-antigen complex and scratching behaviors induced by compound 48/80. The fermented ID more potently inhibited the PCA reaction and scratching behaviors than the non-fermented one. These extracts also inhibited mRNA expression of TNF-alpha and IL-4, as well as NF-kappaB activation in RBL-2H3 cells induced by the IgE-antigen complex. These findings suggest that LAB fermentation improves ID-mediated inhibition of IgE-induced allergic diseases such as rhinitis and asthma, and that ID works by inhibiting degranulation and NF-kB activation in mast cells and basophils.
Assuntos
Antialérgicos/administração & dosagem , Asteraceae/metabolismo , Bifidobacterium/metabolismo , Fermentação , Hipersensibilidade Imediata/tratamento farmacológico , Lactobacillus acidophilus/metabolismo , Preparações de Plantas/administração & dosagem , Animais , Antialérgicos/imunologia , Antialérgicos/metabolismo , Antialérgicos/uso terapêutico , Asteraceae/imunologia , Comportamento Animal/efeitos dos fármacos , Degranulação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Citocinas/antagonistas & inibidores , Citocinas/metabolismo , Humanos , Hipersensibilidade Imediata/genética , Hipersensibilidade Imediata/metabolismo , Coreia (Geográfico) , Masculino , Camundongos , NF-kappa B/antagonistas & inibidores , NF-kappa B/genética , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/metabolismo , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Preparações de Plantas/imunologia , Preparações de Plantas/metabolismo , Preparações de Plantas/uso terapêutico , Ratos , Ativação Transcricional/efeitos dos fármacosRESUMO
The immediate-type allergic reaction is involved in many allergic diseases such as asthma and allergic rhinitis. The discovery of drugs for the treatment of immediate-type allergic diseases is a very important subject in human health. In this study, we investigated the effect of Artemisia iwayomogi (AIAE) on mast cell-mediated allergic reaction and inflammatory cytokine secretion. AIAE inhibited compound 48/80-induced systemic reactions in mice. AIAE decreased the passive cutaneous anaphylaxis (PCA) reaction activated by antidinitrophenyl (anti-DNP) IgE antibody. AIAE dose-dependently reduced histamine release from rat peritoneal mast cells activated by compound 48/80 or anti-DNP IgE. Furthermore, AIAE attenuated the phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated tumor necrosis factor-alpha and interleukin-6 secretion in human mast cells. These results provide evidence that AIAE may be beneficial in the treatment of allergic diseases.
Assuntos
Artemisia/química , Citocinas/metabolismo , Hipersensibilidade Imediata/prevenção & controle , Extratos Vegetais/farmacologia , Animais , Calcimicina/farmacologia , Linhagem Celular Tumoral , Liberação de Histamina/efeitos dos fármacos , Humanos , Hipersensibilidade Imediata/induzido quimicamente , Hipersensibilidade Imediata/metabolismo , Imunoglobulina E/administração & dosagem , Imunoglobulina E/imunologia , Masculino , Mastócitos/citologia , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Ratos , Ratos Sprague-Dawley , Acetato de Tetradecanoilforbol/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , p-Metoxi-N-metilfenetilamina/administração & dosagem , p-Metoxi-N-metilfenetilamina/toxicidadeRESUMO
BACKGROUND: Modified allergen extracts (allergoids) with reduced IgE-binding capacity are successfully used in immunotherapy of atopic allergy. Their reduced T-cell stimulatory capacity is less well studied and is a subject of the present study. METHODS: We compared the ability of native house dust mite extract (Dermatophagoides pteronyssinus; HDM) and the glutaraldehyde-modified allergoid (HDM-GA) to induce the proliferation and cytokine production by fresh PBMC and by DC-stimulated polyclonal Th cells and HDM-specific Th cell clones. RESULTS: Freshly isolated T cells showed a partially reduced responsiveness to HDM-GA, differentially pronounced in different donors. HDM-specific Th cell clones prepared from three donors showed either a complete loss of reactivity to HDM-GA, or completely preserved responsiveness. The frequency of nonreactive clones was donor-dependent (2/3, 3/10 and 1/10). GA modification of HDM did not interfere with the cytokine production profile of HDM-specific T cell clones. CONCLUSIONS: The reduced stimulatory potential of HDM-GA results mainly from a loss of certain Th cell epitopes, rather than impaired allergen uptake and presentation, or induction of suppressive factors. Varying frequencies of allergoid-nonreactive HDM-specific Th cells may result in differential responses of individual patients to immunotherapy.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Dermatophagoides pteronyssinus/imunologia , Extratos Vegetais/imunologia , Alérgenos/imunologia , Alergoides , Animais , Divisão Celular/imunologia , Reações Cruzadas/imunologia , Citocinas/imunologia , Citocinas/metabolismo , Epitopos de Linfócito T/imunologia , Hipersensibilidade Imediata/imunologia , Hipersensibilidade Imediata/metabolismo , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Monócitos/imunologiaRESUMO
The relationship between breast-feeding, IgA production and development of atopic disease in children is a matter of controversy. Some of this controversy might be due to individual differences in the composition of breast milk. The aim of this study was to relate the levels of cytokines, chemokines and secretory (S)-IgA antibodies in breast milk to the development of atopic manifestation and salivary IgA production in infants. Cytokine, chemokine and SIgA levels, as measured with enzyme-linked immunosorbent assay (ELISA), in colostrum and mature milk were analyzed in relation to the development of positive skin-prick tests (SPT), allergic symptoms and salivary IgA antibody production during the first 2 years of life in 53 infants. There was no association between levels of IL-4, -5, -6, -8, -10, -13, -16, IFN-gamma, TGF-beta1, -beta2, RANTES, eotaxin or SIgA levels in the breast milk with either SPT-positivity, development of allergic symptoms or salivary IgA levels during the first 2 years of life in the infants. Thus, differences in the composition of cytokines, chemokines and SIgA in breast milk did not, to any major degree, affect the development of a positive SPT, atopic symptoms, nor salivary IgA antibody production during the first 2 years of life.