epiglucan and Asthma

House dust mites (HDM; Dermatophagoides sp.) are one of the commonest aeroallergens worldwide and up to 85% of asthmatics are typically HDM allergic. Allergenicity is associated both with the mites themselves and with ligands derived from mite-associated bacterial and fungal products. Murine models of allergic airways disease for asthma research have recently switched from the use of surrogate allergen ovalbumin together with adjuvant to use of the HDM extract. This has accelerated understanding of how adaptive and innate immunity generate downstream pathology. We review the myriad ways in which HDM allergic responses are orchestrated. Understanding the molecular pathways that elicit HDM-associated pathology is likely to reveal novel targets for therapeutic intervention.

Topics: Adrenal Cortex Hormones; Allergens; Animals; Antigens, Dermatophagoides; Asthma; beta-Glucans; Bronchi; Bronchial Hyperreactivity; Chitin; Cytokines; Dendritic Cells; Disease Models, Animal; Epithelial Cells; Humans; Immunotherapy; Mice; Pyroglyphidae; Respiratory Mucosa; Spores, Fungal; Toll-Like Receptors

(1-->3)-beta-D-glucan is a polyglucose structure in the cell wall of moulds, some bacteria and plants. Due to its unique (1-->3)-beta linkage it binds to specific receptors on phagocytosing cells and induces changes in their metabolism. Under realistic environmental concentrations, available data suggest that these changes express themselves as alterations of the defense mechanisms to other agents. Inhalation of (1-->3)-beta-D-glucan in humans causes symptoms from the upper respiratory tract and induction of cytokines in blood monocytes. (1-->3)-beta-D-glucan can be used as a marker of mould biomass in field studies. Relationships between the amount of (1-->3)-beta-D-glucan and the extent of symptoms as well as lung function changes and inflammatory markers have been described. In view of the mechanisms involved in the normal development of the immune system, children seem to be a particular group at risk due to (1-->3)-beta-D-glucan exposure.

Topics: Air Pollution, Indoor; Animals; Asthma; beta-Glucans; Glucans; Humans; Hypersensitivity; Immunity

The aim of this study was to assess the cytokine response after nasal exposure to organic dusts. In a double blinded, crossover study five garbage workers with occupational airway symptoms and five healthy garbage workers were intranasally exposed to endotoxin (lipopolysaccharide LPS), beta-1,3-D-glucan (GLU), Aspergillus sp., compost or the saline dilute for 15 min. Nasal cavity volume and nasal lavage (NAL) were performed at baseline and 3, 6, 11 h postexposure. NAL was analysed with differential cell counts, cysteinyl-leukotrienes, tumour necrosis factor alpha, interleukin (IL)-1beta, IL-6 and IL-8. A whole blood assay on cytokine-release was performed with LPS and GLU. NAL cytokines neutrophils, lymphocytes and albumin increased significantly at 6 h after LPS exposure. GLU induced an increase in albumin and a slight increase in IL-1beta 6-11 h post exposure. In the WBA a significant increase in all cytokines after exposure to LPS as well as GLU was found. Significantly more cells were seen in NAL of the control group 6 h post LPS exposure. In conclusion lipopolysaccharide is the most potent inducer of inflammation in the nasal mucosa whereas compost and beta-1,3-D-glucan only induce minor changes. This reaction to lipopolysaccharide is attenuated in workers with occupational airway symptoms. In whole blood assay, however, beta-1,3-D-glucan also induces cytokine release, indicating a different protective effect of the nasal mucosa towards lipopolysaccharide and beta-1,3-D-glucan.

Topics: Allergens; Aspergillus; Asthma; beta-Glucans; Cross-Over Studies; Cytokines; Double-Blind Method; Dust; Female; Glucans; Humans; Interleukins; Leukotrienes; Lipopolysaccharides; Male; Nasal Lavage Fluid; Nasal Mucosa; Occupational Diseases; Occupational Exposure; Refuse Disposal; Tumor Necrosis Factor-alpha

Asthma is one of the most common chronic diseases. In many cases it is preceded by the development of an immune response to allergens such as animal fur, dust, pollens and etc. In human population this disease is heterogeneous, and no selective drugs are available at the moment for some endotypes of asthma. The role of the adaptive immune system in the pathogenesis of asthma was extensively studied, while the role of innate immune cells, in particular myeloid cells, was not sufficiently addressed. Myeloid cells, such as macrophages and dendritic cells, are characterized by high plasticity, heterogenicity and ability to undergo polarization in response to various pathogenic stimuli, including those engaging innate immune receptors. Recently, special attention was drawn to the link between polarization of macrophages and cell metabolism. We hypothesized that immunometabolic reprogramming of myeloid cells, in particular, of macrophages and dendritic cells during sensitization with an allergen may affect further immune response and asthma development. To test this hypothesis, we generated distinct types of myeloid cells in vitro from murine bone marrow and analyzed their immunometabolic profiles upon activation with house dust mite extract (HDM) and its key active components. We found that the combination of lipopolysaccharide (LPS) and beta-glucan is sufficient to upregulate proinflammatory cytokine production as well as respiratory and glycolytic capacity of myeloid cells, comparably to HDM. This specific immunometabolic phenotype was associated with altered mitochondrial morphology and possibly with increased ROS production in macrophages. Moreover, we found that both TNF production and metabolic remodeling of macrophages in response to HDM are TLR4-dependent processes. Altogether, these results expand our understanding of molecular mechanisms underlying asthma induction and pathogenesis and may potentially lead to new therapeutic strategies for the treatment of this disease.

Topics: Allergens; Animals; Asthma; beta-Glucans; Cytokines; Dust; Humans; Lipopolysaccharides; Macrophages; Mice; Phenotype; Pyroglyphidae; Reactive Oxygen Species; Toll-Like Receptor 4

Allergen-specific immunotherapy via the skin targets a tissue rich in antigen-presenting cells, but can be associated with local and systemic side effects. Allergen-polysaccharide neoglycogonjugates increase immunization efficacy by targeting and activating dendritic cells via C-type lectin receptors and reduce side effects.. We investigated the immunogenicity, allergenicity, and therapeutic efficacy of laminarin-ovalbumin neoglycoconjugates (LamOVA).. The biological activity of LamOVA was characterized in vitro using bone marrow-derived dendritic cells. Immunogenicity and therapeutic efficacy were analyzed in BALB/c mice. Epicutaneous immunotherapy (EPIT) was performed using fractional infrared laser ablation to generate micropores in the skin, and the effects of LamOVA on blocking IgG, IgE, cellular composition of BAL, lung, and spleen, lung function, and T-cell polarization were assessed.. Conjugation of laminarin to ovalbumin reduced its IgE binding capacity fivefold and increased its immunogenicity threefold in terms of IgG generation. EPIT with LamOVA induced significantly higher IgG levels than OVA, matching the levels induced by s.c. injection of OVA/alum (SCIT). EPIT was equally effective as SCIT in terms of blocking IgG induction and suppression of lung inflammation and airway hyperresponsiveness, but SCIT was associated with higher levels of therapy-induced IgE and TH2 cytokines. EPIT with LamOVA induced significantly lower local skin reactions during therapy compared to unconjugated OVA.. Conjugation of ovalbumin to laminarin increased its immunogenicity while at the same time reducing local side effects. LamOVA EPIT via laser-generated micropores is safe and equally effective compared to SCIT with alum, without the need for adjuvant.

Topics: Allergens; Animals; Asthma; beta-Glucans; Lasers; Mice; Mice, Inbred BALB C; Ovalbumin; Pneumonia

Asthma severity can be affected by microbial exposures. However, less is known about the specific indoor agents aggravating the disease in children. We examined the associations between indoor endotoxin and beta-(1 → 3)-D-glucan exposures and asthma severity in children with asthma.. A clinical cross-sectional study of schoolchildren (aged 7-17 years) was conducted in the province of Saskatchewan, Canada. Children with asthma (n = 116) were identified from 335 participants using a combination of survey responses and objective clinical assessments. We then ascertained asthma severity based on recommended guidelines (continuous daytime asthma symptoms, frequent nighttime asthma symptoms, and ≤ 60% predicted FEV. The study population of 116 children with asthma was comprised of 75.9% mild asthma and 24.1% moderate/severe asthma. Higher mattress endotoxin concentration was associated with increased odds of moderate/severe asthma [adjusted odds ratio (aOR) = 11.40, 95% confidence interval (CI): 1.45-89.43] while higher beta-(1 → 3)-D-glucan concentration (aOR = 0.16, 95% CI: 0.03-0.89) and load (aOR = 0.10, 95% CI: 0.02-0.72) in play areas were inversely associated with moderate/severe asthma. Furthermore, higher mattress endotoxin concentration was associated with lower FVC (p = 0.01) and FEV. Our results showed differential effects of microbial exposures on childhood asthma severity and further highlight domestic endotoxin exposure effects on respiratory health outcomes in children with asthma.

Topics: Adolescent; Air Pollution, Indoor; Asthma; Beds; beta-Glucans; Child; Cross-Sectional Studies; Dust; Endotoxins; Exercise Test; Female; Forced Expiratory Volume; Humans; Male; Proteoglycans; Severity of Illness Index; Spirometry; Vital Capacity

β-(1,3)-Glucan is present in mould cell walls and frequently detected in house dust mite (HDM) faeces. β-Glucan exposure is thought to be associated with pulmonary allergic inflammation in mouse and man, although the published data are inconsistent. Here, we show that highly purified β-glucan exacerbates HDM-induced eosinophilic, T helper 2 type airway responses by acting as an adjuvant, promoting activation, proliferation and polarisation of HDM-specific T cells (1-Derβ T cells). We therefore provide definitive evidence that β-glucan can influence allergic pulmonary inflammation.

Topics: Animals; Antigens, Dermatophagoides; Asthma; beta-Glucans; Drug Synergism; Environmental Exposure; Mice; Mice, Inbred C57BL; Mycotoxins

Topics: Asthma; beta-Glucans; Eczema; Ergosterol; Fungi; Humans; Rhinitis

Inverse associations have been found between exposure to bio-contaminants and asthma and allergies. The aim of this study was to prospectively assess whether early exposure to bio-contaminants in dust is associated with asthma and allergy later in childhood among children from (sub)-urban areas. In subsets of three European birth cohorts (PIAMA: n=553; INMA: n=481; and LISAplus: n=395), endotoxin, (1,3,)-β-d-glucan and extracellular polysaccharide were measured in dust from living rooms shortly after birth. Current asthma at 6 years and 10 years of age and ever asthma up to 10 years of age were assessed by parental questionnaires. Specific IgE levels at 8 years (PIAMA) and 10 years (LISAplus) were available. Adjusted, cohort-specific logistic regression analyses were performed. Higher endotoxin concentrations were positively associated with current asthma at 6 years of age in PIAMA (adjusted OR 1.96, 95% CI 1.07-3.58), but were inversely related with ever asthma up to 10 years of age in INMA (adjusted OR 0.39, 95% CI 0.16-0.94). No associations with asthma were found for LISAplus. No associations were observed with atopic sensitisation in all cohorts. All associations with (1,3)-β-d-glucan and extracellular polysaccharide were statistically nonsignificant. The suggested immunological mechanisms of early exposure to bio-contaminants with regards to asthma and allergy might be different for children growing up in (sub)-urban environments.

Topics: Air Pollutants; Allergens; Asthma; beta-Glucans; Child; Dust; Endotoxins; Environmental Exposure; Europe; Female; Geography; Humans; Hypersensitivity; Hypersensitivity, Immediate; Immunoglobulin E; Infant, Newborn; Logistic Models; Male; Polysaccharides; Prospective Studies; Proteoglycans; Surveys and Questionnaires; Urban Population

Topics: Asthma; beta-Glucans; Eczema; Ergosterol; Fungi; Humans; Rhinitis

To investigate the modulation of B-cell-activating factor (BAFF) expression on the basophil membrane of allergic patients. BAFF is an important regulator of B-cell activation, proliferation and immunoglobulin production, which may play a role in respiratory allergic diseases in promoting the production of IgE by B cells.. Peripheral blood samples of 10 patients with allergic rhinitis, 3 with severe asthma and fungal sensitization (SAFS), 3 with allergic bronchopulmonary aspergillosis (ABPA) and 11 healthy controls were assessed regarding BAFF (CD257) expression using the basophil activation test before and after stimulation with IgE and allergens, as well IgE-independent stimuli, like fMLP, lipotheichoic acid from Staphylococcus aureus (LTA-SA) and lipopolysaccharide (LPS).. BAFF membrane expression did not change after IgE and allergen stimulation both in patients and controls, while it was upregulated by Aspergillus stimulation, both in sensitized patients and controls. In both patients and controls, BAFF expression was significantly upregulated following LTA-SA and β-1,3-glucan exposure (toll-like receptor-2 ligands), but not following LPS stimulation.. Basophils from allergic and healthy subjects constitutively express membrane BAFF, which is not upregulated by IgE or specific allergens but by TLR-2 ligands (LTA-SA and β-1,3-glucan). Aspergillus fumigatus stimulation was able to upregulate BAFF expression on the basophils of sensitized asthmatic patients, but not via IgE-dependent mechanisms, since results did not differ between the patient and control groups. These findings suggest that basophils may contribute to the polyclonal production of IgE commonly observed in patients with SAFS and ABPA.

Topics: Adult; Aspergillosis, Allergic Bronchopulmonary; Aspergillus fumigatus; Asthma; B-Cell Activating Factor; B-Lymphocytes; Basophils; beta-Glucans; Female; Humans; Immunoglobulin E; Lipopolysaccharides; Lymphocyte Activation; Male; Membrane Proteins; Middle Aged; Rhinitis, Allergic; Tetraspanin 30; Toll-Like Receptor 2; Up-Regulation

Asthma is a heterogeneous disease whose etiology is poorly understood but is likely to involve innate responses to inhaled microbial components that are found in allergens. The influence of these components on pulmonary inflammation has been largely studied in the context of individual agonists, despite knowledge that they can have synergistic effects when used in combination. Here we have explored the effects of LPS and β-glucan, two commonly-encountered microbial agonists, on the pathogenesis of allergic and non-allergic respiratory responses to house dust mite allergen. Notably, sensitization with these microbial components in combination acted synergistically to promote robust neutrophilic inflammation, which involved both Dectin-1 and TLR-4. This pulmonary neutrophilic inflammation was corticosteroid-refractory, resembling that found in patients with severe asthma. Thus our results provide key new insights into how microbial components influence the development of respiratory pathology.

Topics: Animals; Asthma; beta-Glucans; Disease Models, Animal; Drug Resistance; Inflammation; Lipopolysaccharides; Mice, Knockout; Neutrophil Infiltration; Neutrophils; Pyroglyphidae; Steroids; Th17 Cells; Th2 Cells

Qualitative reporting of home indoor moisture problems predicts respiratory diseases. However, causal agents underlying such qualitative markers remain unknown. In the homes of 198 multiple allergic case children and 202 controls in Sweden, we cultivated culturable fungi by directly plating dust, and quantified (1-3, 1-6)-β-D-glucan and ergosterol in dust samples from the child's bedroom. We examined the relationship between these fungal agents and degree of parent or inspector-reported home indoor dampness, and microbiological laboratory's mold index. We also compared the concentrations of these agents between multiple allergic cases and healthy controls, as well as IgE-sensitization among cases. The concentrations of culturable fungal agents were comparable between houses with parent and inspector-reported mold issues and those without. There were no differences in concentrations of the individual or the total summed culturable fungi, (1-3, 1-6)-β-D-glucan, and ergosterol between the controls and the multiple allergic case children, or individual diagnosis of asthma, rhinitis, or eczema. Culturable fungi, (1-3, 1-6)-β-D-glucan, and ergosterol in dust were not associated with qualitative markers of indoor dampness or mold or indoor humidity. Furthermore, these agents in dust samples were not associated with any health outcomes in the children.

Topics: Asthma; beta-Glucans; Case-Control Studies; Child; Child, Preschool; Dust; Eczema; Ergosterol; Fungi; Housing; Humans; Infant; Rhinitis

Topics: Asthma; beta-Glucans; Eczema; Ergosterol; Fungi; Humans; Rhinitis

Topics: Asthma; beta-Glucans; Eczema; Ergosterol; Fungi; Humans; Rhinitis

Much scientific evidence indicates a positive association between moldy environments and respiratory illnesses and/or symptoms (e.g., asthma). Recently, submicron fungal fragments (<1.0 μm) have been suggested as a potential contributor to adverse health effects due to their biological composition (e.g., antigens, mycotoxins, and (1,3)-β-D-glucan) as well as their small size. However, the contribution of exposure to fine fungal particles on adverse health outcomes has been poorly characterized, particularly in homes with asthmatic children. We characterized the airborne level of smaller-sized fungal particles between homes with and without asthmatic children.. We visited 29 homes with (n=15) and without (n=14) an asthmatic child and sampled submicron fungal fragments in a living room and child׳s bedroom, along with outdoor sampling, using the NIOSH two-stage sampler. (1,3)-β-D-glucan of fungal fragments analyzed by Limulus Amebocyte lysate assay (LAL) was used for quantifying their exposure.. Overall, the geometric mean (GM) concentration of (1,3)-β-D-glucan in submicron fungal fragments in indoor air was two-fold higher in homes with asthmatic children (50.9 pg/m(3)) compared to homes with non-asthmatic children (26.7 pg/m(3)) (P<0.001). The GM concentration of these particles in child׳s bedroom in homes with an asthmatic child (66.1 pg/m(3)) was about three times higher than that in homes with non-asthmatic children (23.0 pg/m(3)) (P<0.001). The relative humidity had a negative correlation with the concentration of (1,3)-β-D-glucan in submicron fungal fragments (Pearson coefficient=-0.257, P=0.046).. Our findings indicate that homes with asthmatic children have a higher concentration of submicron fungal fragments compared to homes with non-asthmatic children. A greater exposure to smaller-sized fungal particles may occur in homes with an asthmatic child as relative humidity decreases. The very careful control of relative humidity in indoor air is necessary for reducing exposure to fine fungal particles and inhibiting the growth of microorganisms in homes with allergic diseases.

Topics: Asthma; beta-Glucans; Child; Female; Fungi; Housing; Humans; Humidity; Male; Particulate Matter; Proteoglycans

Mould exposure has been linked to childhood asthma and bronchial hyper-responsiveness. Few studies have assessed beta-(1,3)-d-glucan (beta-glucan), a significant fungal cell wall constituent, in relation to asthma in adolescence.. To determine whether house dust-derived beta-glucan exposure at age 7-10 is associated with the development and persistence of atopic and non-atopic asthma, and bronchial hyper-responsiveness (BHR) by age 11-14.. Dust samples were collected from the 1995 Study of Asthma, Genes, and Environment (SAGE) birth cohort. This cohort was derived from Manitoba provincial healthcare administrative records of children high and low risk for asthma. Samples were collected from the homes of 422 children at age 7-10 and analyzed using beta-glucan and endotoxin-specific Limulus Amoebocyte Lysate assays. Asthma, atopy, and BHR status of each child were also assessed at ages 7-10 and 11-14.. At age 7-10, beta-glucan dust levels in the home were associated with persistent atopic asthma at age 11-14 (OR 1.79 for each unit increase in levels, 95% CI 1.14-2.81), independent of endotoxin exposure, and Alternaria or Cladosporium sensitization. The likelihood of BHR almost doubled with unit increases in dust beta-glucan in asthmatic children. In children without asthma, exposure to high beta-glucan levels at age 7-10 also elevated risk for BHR in adolescence (OR 1.74, 95% CI 1.05-2.89). New-onset atopic asthma was twice more likely following high beta-glucan exposure in children without asthma but the association did not reach statistical significance. No associations were evident with concurrent asthma phenotype at age 7-10 or non-atopic asthma at age 11-14.. These findings implicate home beta-glucan exposure at school-age as a risk factor for persistent atopic asthma and new-onset BHR. The higher prevalence of BHR in urban adolescents may be propagated by this home exposure.

Topics: Adolescent; Age Factors; Asthma; beta-Glucans; Bronchial Hyperreactivity; Child; Dust; Endotoxins; Environmental Exposure; Female; Humans; Longitudinal Studies; Male; Phenotype; Prevalence; Proteoglycans

It is well accepted that mold exposure is a major contributor to the development of asthma, and beta-glucans are often used as a surrogate for mold exposure in the environment. Beta-glucans are an important component of mold spores and are recognized by the immune system by their receptor, Dectin-1. Cladosporium cladosporioides spores have a high beta-glucan content, but the beta-glucans are not available on the surface of live spores.. We sought to determine whether altering the exposure of beta-glucans in C cladosporioides through heat killing could alter the immune response through binding to Dectin-1.. In a murine model of mold-induced asthma, mice were repeatedly exposed to either live or heat-killed C cladosporioides and the phenotype was determined by the measurement of airway hyperresponsiveness, airway inflammation, and cytokine production. Pro-inflammatory cytokines from dendritic cells were measured by using quantitative PCR and ELISA.. Live C cladosporioides induced robust airway hyperresponsiveness, eosinophilia, and a predominately TH2 response, while heat-killed C cladosporioides induced a strong TH17 response and neutrophilic inflammation, but very mild airway hyperresponsiveness. Heat killing of C cladosporioides spores effectively exposed beta-glucans on the surface of the spores and increased binding to Dectin-1. In the absence of Dectin-1, heat-killed spores induced a predominantly TH2 response analogous to live spores. Furthermore, the production of TH17-skewing IL-6, IL-23, and TNF-α by dendritic cells in response to heat-killed C cladosporioides was dependent on Dectin-1.. The host immune response to C cladosporioides is dependent on the surface availability of beta-glucans rather than the total beta-glucan content.

Topics: Animals; Asthma; beta-Glucans; Cladosporium; Cytokines; Dendritic Cells; Lectins, C-Type; Lung; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neutrophils; Spores, Fungal; Th17 Cells; Th2 Cells

People living in damp buildings are typically exposed to spore and mycelial fragments of the fungi that grow on damp building materials. There is experimental evidence that this exposure to triple-helical (1, 3)-β-D glucan and low molecular weight toxins may be associated with non-atopic asthma observed in damp and moldy buildings. However, the mechanisms underlying this response are only partially resolved. Using the pure (1, 3)-β-D glucan, curdlan, and the murine macrophage cell line, RAW 264.7, there were two objectives of this study. The first was to determine whether signal transduction pathways activating asthma-associated cell signaling pathways were stimulated using mouse transduction Pathway Finder(®) arrays and quantitative real-time (QRT) PCR. The second objective was to evaluate the dose and temporal responses associated with transcriptional changes in asthma-associated cytokines, the signal transduction receptor gene Dectin-1, and various transcription factor genes related to the induction of asthma using customized RT-PCR-based arrays. Compared to controls, the 10(-7) M curdlan treatment induced significant changes in gene transcription predominately in the NFkB, TGF-β, p53, JAK/STAT, P13/AKT, phospholipase C, and stress signaling pathways. The 10(-8) M curdlan treatment mainly induced NFkB and TGF-β pathways. Compared to controls, curdlan exposures also induced significant dose- and time-dependent changes in the gene translations. We found that that curdlan as a non-allergenic potentiator modulates a network of transduction signaling pathways not only associated with TH-1, TH-2, and TH-3 cell responses including asthma potentiation, but a variety of other cell responses in RAW 264.7 cells. These results help provide mechanistic basis for some of the phenotypic changes associated with asthma that have been observed in in vitro, in vivo, and human studies and open up a hypothesis-building process that could explain the rise of non-atopic asthma associated with fungi.

Topics: Animals; Asthma; beta-Glucans; Cell Line; Cytokines; Dose-Response Relationship, Drug; Lectins, C-Type; Macrophages; Mice; NF-kappa B; Real-Time Polymerase Chain Reaction; Signal Transduction; Time Factors; Transcription, Genetic; Transforming Growth Factor beta

Allergic rhinitis (AR) and asthma are 2 entities of allergic airway diseases that frequently occur together, which is referred to as united airways. In contrast to this general concept, we hypothesized that innate immunity of the upper and lower airways is respectively distinctive, because the immunologic conditions of the nasal and lung mucosa as well as the functions of the immune cells within their epithelia are different.. We wanted to identify distinctive mechanisms of innate immunity in the nose and lung mucosa, which are responsible for house dust mite (HDM)-induced AR and allergic asthma (AA), respectively.. We constructed a mouse model of AR or AA induced by sensitization and consequent provocation with HDM extracts.. HDM-derived β-glucans, rather than LPS, were proven to be essential to activating innate immunity in the nasal mucosa and triggering AR, which depended on Toll-like receptor 2 (TLR2), but not on TLR4; however, the LPS/TLR4 signaling axis, rather than β-glucans/TLR2, was critical to HDM-induced AA. These differences were attributed to the specific role of β-glucans and LPS in inducing the surface expression of TLR2 and TLR4 and their translocation to lipid rafts in nasal and bronchial epithelial cells, respectively. We also showed that dual oxidase 2-generated reactive oxygen species mediate both β-glucan-induced TLR2 activation and LPS-induced TLR4 activation.. We describe a novel finding of distinctive innate immunity of the nose and lungs, respectively, which trigger AR and AA, by showing the critical role of HDM-induced TLR activation via dual oxidase 2-mediated reactive oxygen species.

Topics: Animals; Asthma; beta-Glucans; Dual Oxidases; Epithelial Cells; Hypersensitivity; Immunity, Innate; Lipopolysaccharides; Lung; Mice; NADPH Oxidases; Nasal Mucosa; Pyroglyphidae; Reactive Oxygen Species; Respiratory Mucosa; Respiratory System; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Toll-Like Receptor 2; Toll-Like Receptor 4

The objective of this study is to detect the effect of beta-glucan derived from Aureobasidium pullulans SM-2001, a UV induced mutant of A. pullulans on the ovalbumin (OVA) induced allergic asthma. The test articles were orally administered to OVA-inducing asthmatic mice 4 days after sensitization for 13 days at 31.25, 62.5 or 125 mg/kg levels. Three days after the OVA sensitization, ten mice were selected per group based on body weight and were sacrificed three days after the OVA aerosol challenge. The changes on the body weight, lung weight, total leukocytes in peripheral blood and total cells in bronchoalveolar lavage fluid (BALF) were observed with changes on the lung histopathology and histomorphometry. The results were compared with dexamethasone (DEXA) 3 mg/kg intraperitoneally treated mice. The results showed increases of body weight after the OVA aerosol challenge, lung weight, total leukocytes and eosinophils in peripheral blood, total cell numbers, neutrophil and eosinophils in BALF were detected in the OVA control compared to sham control (non-OVA). However, these changes from asthmatic responses were significantly or dose-dependently decreased in the beta-glucan-dosing groups compared to those of the OVA control. Therefore, it is concluded that beta-glucan has favorable effects on asthmatic response induced by OVA. It was found that beta-glucan 125 mg/kg showed similar or slightly lower efficacy compared with DEXA 3 mg/kg.

Topics: Animals; Anti-Asthmatic Agents; Ascomycota; Asthma; beta-Glucans; Body Weight; Bronchoalveolar Lavage Fluid; Dexamethasone; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Glucocorticoids; Leukocyte Count; Leukocytes; Lung; Mice; Mice, Inbred BALB C; Ovalbumin

There is considerable evidence supporting a role for mold exposure in the pathogenesis and expression of childhood asthma. Aspergillus versicolor and Cladosporium cladosporioides are common molds that have been implicated in asthma. In a model of mold-induced asthma, mice were repeatedly exposed to either A. versicolor or C. cladosporioides spores. The two molds induced distinct phenotypes, and this effect was observed in both BALB/c and C57BL/6 strains. C. cladosporioides induced robust airway hyperresponsiveness (AHR), eosinophilia, and a predominately Th2 response, whereas A. versicolor induced a strong Th17 response and neutrophilic inflammation, but very mild AHR. Neutralization of IL-17A resulted in strong AHR and eosinophilic inflammation following A. versicolor exposure. In Dectin-1-deficient mice, A. versicolor exposure resulted in markedly attenuated IL-17A and robust AHR compared with wild-type mice. In contrast, C. cladosporioides induced AHR and eosinophilic inflammation independent of IL-17A and Dectin-1. A. versicolor, but not C. cladosporioides, spores had increased exposure of β-glucans on their surface and were able to bind Dectin-1. Thus, the host response to C. cladosporioides was IL-17A- and Dectin-1-independent, whereas Dectin-1- and IL-17A-dependent pathways were protective against the development of asthma after exposure to A. versicolor.

Topics: Animals; Anti-Asthmatic Agents; Aspergillus; Asthma; beta-Glucans; Bronchial Hyperreactivity; Cladosporium; Eosinophils; Immunophenotyping; Inflammation Mediators; Interleukin-17; Lectins, C-Type; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Neutrophils; Spores, Fungal; Surface Properties

For a long time, exposure to mould and dampness-derived microbial components was considered a risk factor for the development of respiratory diseases and symptoms. Some recent studies suggested that early childhood exposure to mould components, such as (1,3)-β-D-glucan and extracellular polysaccharides (EPSs), may protect children from developing allergy. We investigated the association of exposure to (1,3)-β-D-glucan, EPS and endotoxin with asthma and allergies in 6-yr-old children. This investigation was the follow-up to a nested case-control study among three European birth cohorts. Children from two ongoing birth cohort studies performed in Germany (n = 358) and one in the Netherlands (n = 338) were selected. Levels of (1,3)-β-D-glucan, EPS and endotoxin were measured in settled house dust sampled from children's mattresses and living-room floors when the children were, on average, 5 yrs of age. At the age of 6 yrs, health outcome information was available for 678 children. In the two German subsets, domestic EPS and endotoxin exposure from children's mattresses were significantly negatively associated with physician-diagnosed asthma (OR per interquartile range increase 0.60 (95% CI 0.39-0.92) and 0.55 (95% CI 0.31-0.97), respectively). In addition, EPS exposure was inversely related to physician-diagnosed allergic rhinitis (OR 0.50, 95% CI 0.31-0.81). For the Dutch population, no associations were observed between exposure to microbial agents and respiratory health outcomes. We found inverse associations between domestic exposure to EPS and endotoxin from children's mattresses, and doctor-diagnosed asthma and rhinitis in German, but not in Dutch, school children. The reasons for the differences between countries are not clear.

Topics: Asthma; Beds; beta-Glucans; Case-Control Studies; Child; Child, Preschool; Cohort Studies; Dust; Female; Floors and Floorcoverings; Fungi; Germany; Humans; Male; Netherlands; Proteoglycans; Rhinitis, Allergic, Perennial; Toxins, Biological

In addition to immune cells, airway epithelial cells can contribute to and shape the immune response in the lung by secreting specific cytokines. IL-6 is a key factor in determining the effector fate of CD4(+) T cells. Here we show that under basal conditions, the IL-6 gene is already highly expressed in lung epithelial cells, but not in immune cells resident in the lung. However, upon exposure of the lungs to fungal allergens, the direct contact of β-glucans present in the fungus cell wall with lung epithelial cells is sufficient to trigger the rapid synthesis and secretion of IL-6 protein. This posttranscriptional regulation of IL-6 in response to fungal extracts is mediated by the p38 mitogen-activated protein kinase pathway. The inhalation of β-glucans with a nonallergenic antigen is sufficient to provide an adjuvant effect that leads to mucous hyperplasia in the airways. Thus, β-glucans may constitute a common determinant of the fungal and plant-derived allergens responsible for some of the pathological features in allergic asthma.

Topics: Allergens; Animals; Aspergillus fumigatus; Asthma; beta-Glucans; CD4-Positive T-Lymphocytes; Cells, Cultured; Epithelial Cells; Gene Expression Regulation; Interleukin-6; Lung; MAP Kinase Signaling System; Mice; Mice, Knockout; p38 Mitogen-Activated Protein Kinases; Respiratory Mucosa

Associations between house dust-associated beta-(1,3)-glucan exposure and airway inflammatory reactions have been reported, while such exposures in early childhood have been suggested to protect against asthma and wheezing. Most epidemiological studies have used reservoir dust samples and an inhibition enzyme immunoassay (EIA) for beta-(1,3)-glucan exposure assessment. The objective of this study was to develop inexpensive but highly sensitive enzyme immunoassays to measure airborne beta-(1,3)-glucans in low-exposure environments, like homes. Specificities of available anti-beta-(1,3)-glucan antibodies were defined by direct and inhibition experiments. Three suitable antibody combinations were selected for sandwich EIAs. beta-(1,3)-Glucans in passive airborne dust collected with an electrostatic dust fall collector (EDC) and floor dust from seven homes were measured with the three EIAs. Floor dust samples were additionally analyzed in the inhibition EIA. The sandwich EIAs were sensitive enough for airborne glucan measurement and showed different specificities for commercial glucans, while the beta-(1,3)-glucan levels in house dust samples correlated strongly. The feasibility of measuring glucans in airborne dust with the recently introduced EDC method was further investigated by selecting the most suitable of the three EIAs to measure and compare beta-(1,3)-glucan levels in the EDC and in floor and actively collected airborne dust samples of the previously performed EDC validation study. The EDC beta-(1,3)-glucan levels correlated moderately with beta-(1,3)-glucans in actively collected airborne dust and floor dust samples, while the glucan levels in the airborne dust and floor dust samples did not correlate. The combination of the newly developed beta-(1,3)-glucan sandwich EIA with EDC sampling now allows assessment in large-scale population studies of exposure to airborne beta-(1,3)-glucans in homes or other low-exposure environments.

Topics: Air Microbiology; Air Pollutants; Air Pollution, Indoor; Antigens, Bacterial; Antigens, Fungal; Antigens, Plant; Asthma; beta-Glucans; Dust; Environmental Exposure; Environmental Monitoring; Housing; Humans; Immunoenzyme Techniques; Inhalation Exposure; Proteoglycans; Static Electricity

Divergent results have been reported regarding early life exposure to indoor environmental agents and the risk of asthma and allergic sensitization later in life.. To assess whether early exposure to indoor allergens, beta(1,3)-glucans and endotoxin modifies the risk of allergic diseases at 10 years of age.. The concentrations of mite, cat and dog allergens, endotoxin and beta(1,3)-glucans were determined in dust from the homes of 260 two-year-old children with lung function measured at birth (tidal flow volume loops) in the Environment and Childhood Asthma study in Oslo. At 10 years, the health status was assessed in a follow-up study including a structured interview of the parents and an extended clinical examination.. Cat and dog keeping at 2 years of age was reported in 6.5% and 5.5% of the families, respectively. Mite allergens were detected in only 4/260 dust samples. The adjusted odds ratio for asthma at age 10 was 1.20 (95% confidence interval: 1.01-1.43) and 1.22 (1.02-1.46) for bronchial hyperresponsiveness (BHR) per 10 microg/g dust increase in cat allergen exposure at 2 years of age. No association was seen with allergic sensitization. Moreover, endotoxin and beta(1,3)-glucan exposure did not modify the risk of asthma or allergic sensitization. None of the measured environmental factors were associated with lung function at 10 years of age or a relative change in lung function from birth.. In a community with a low prevalence of pet keeping and low mite allergen levels, exposure to cat allergens early in life increased the risk of late childhood asthma and BHR, but not the risk of allergic sensitization. No risk modification was seen for dog allergens, endotoxin and beta(1,3)-glucans.

Topics: Allergens; Animals; Animals, Domestic; Asthma; beta-Glucans; Bronchial Hyperreactivity; Cats; Child; Child, Preschool; Dogs; Endotoxins; Environmental Exposure; Female; Follow-Up Studies; Humans; Male; Proteoglycans; Pyroglyphidae; Risk Factors

The main study objective was to compare different methods for assessing mold exposure in conjunction with an epidemiologic study on the development of children's asthma. Homes of 184 children were assessed for mold by visual observations and dust sampling at child's age 1 (Year 1). Similar assessment supplemented with air sampling was conducted in Year 7. Samples were analyzed for endotoxin, (1-3)-β-D-glucan, and fungal spores. The Mold Specific Quantitative Polymerase Chain Reaction assay was used to analyze 36 mold species in dust samples, and the Environmental Relative Moldiness Index (ERMI) was calculated. Homes were categorized based on three criteria: 1) visible mold damage, 2) moldy odor, and 3) ERMI. Even for homes where families had not moved, Year 7 endotoxin and (1-3)-β-d-glucan exposures were significantly higher than those in Year 1 (p<0.001), whereas no difference was seen for ERMI (p=0.78). Microbial concentrations were not consistently associated with visible mold damage categories, but were consistently higher in homes with moldy odor and in homes that had high ERMI. Low correlations between results in air and dust samples indicate different types or durations of potential microbial exposures from dust vs. air. Future analysis will indicate which, if any, of the assessment methods is associated with the development of asthma.

Topics: Air Pollution, Indoor; Asthma; beta-Glucans; Child; Child, Preschool; Dust; Environmental Exposure; Environmental Monitoring; Epidemiological Monitoring; Female; Fungi; Housing; Humans; Infant; Male; Observation; Odorants; Proteoglycans; Smell; Spores, Fungal

Pediatric asthma has many causes and can manifest differently in different children and at different times. Understanding the many factors related to the development and exacerbation of asthma is complicated by the complexity of the many environmental exposures related to asthma development and morbidity. Furthermore, the same environmental exposures that may cause increased symptoms at 1 point in time may be protective when the exposure occurs earlier or at high enough levels. We know that environmental exposures such as allergens, irritants, and pollutants are quite complex in their composition; further examination of this complexity may improve our understanding of this complex and highly prevalent disease.

Topics: Allergens; Asthma; Child; Endotoxins; Environmental Pollutants; Fungi; Glucans; Humans; Immunoglobulin E; Nitrogen Dioxide; Ozone; Particle Size; Randomized Controlled Trials as Topic; Tobacco Smoke Pollution; Ultrafiltration; Vehicle Emissions

Indoor allergens and microbial bio-contaminants play a significant role in asthma symptoms. The aim of the study was to determine levels of house dust mite allergens, bacterial endotoxin, and fungal beta-glucan in homes of 120 asthmatic children in central Taiwan. Dust samples from 120 mattresses (67 double-sided) were analyzed for house dust mite allergens (Der p 1, Der f 1, and Blo t 5), endotoxin, and beta-glucan. Pillows (n = 118) were analyzed for house dust mite allergens only. Kitchen dust samples were analyzed for the cockroach allergen, Bla g 1. Blo t 5 was detected in 9.3% pillows and 82.2% mattresses, Der p 1 in 95.8% pillows and 93.2% mattresses, and Der f 1 in 82.2% pillows and 83.1% mattresses. Geometric mean levels (95% confidence interval) of endotoxin and beta-glucan in mattresses were 108.4 Eu/mg (81.4-144.2) and 25.2 microg/g (22.7-28.0), respectively. House dust mite allergens and endotoxin levels were significantly lower on the bamboo side of 67 mattresses, compared to the inner sprung mattress side. Geometric mean of kitchen Bla g 1 was 0.61 U/g (95% CI: 0.43-0.85). Given the presence of Der p 1, Der f 1 and Blo t 5 in central Taiwan, it is advised to measure allergens of all three house dust mite species to obtain a true index of allergen exposure. Bamboo sides of mattresses had significantly lower house dust mite allergens and endotoxin levels.

Topics: Adolescent; Air Pollution, Indoor; Allergens; Antigens, Dermatophagoides; Antigens, Plant; Arthropod Proteins; Asthma; Bedding and Linens; Beds; beta-Glucans; Child; Child, Preschool; Cysteine Endopeptidases; Dust; Endotoxins; Environmental Exposure; Female; Housing; Humans; Immunoglobulin E; Male; Taiwan

Beta-(1,3)-glucan is pro-inflammatory and has been associated with airway inflammation and respiratory symptoms. This study assessed beta-(1,3)-glucan levels from upper body clothing (jerseys) of 55 subjects. Beta-(1,3)-glucan levels were estimated with a modified Limulusamoebocyte lysate kinetic assay. Beta-(1,3)-glucan levels ranged widely from 2,697 to 162,690 ng/g. Beta-(1,3)-glucan levels were significantly lower from cotton jerseys and from warm water washed jerseys. Thus, jerseys are potentially a significant exposure source of beta-(1,3)-glucan.

Topics: Asthma; beta-Glucans; Clothing; Dust; Humans; Limulus Test

There is still uncertainty about the determinants of atopic eczema (AE). To explain the heterogeneity of the disease, different phenotypes of AE have been suggested.. The cross-sectional PARSIFAL study included 14 893 school-age children of farmers or children attending Steiner schools and their respective reference groups. A detailed questionnaire was completed, and house dust was collected for the measurement of endotoxin and glucans. Atopic sensitization was defined by allergen-specific IgE levels in the serum.. In multivariate analyses, helping with haying was the only variable related to a farming environment having a consistent inverse association with both current symptoms and a doctor's diagnosis of AE [aOR = 0.65 (95% CI: 0.46-0.93) and 0.73 (0.51-1.05)], respectively. Severe lower respiratory tract infections (LRTI) in the first 2 years of life and usage of antibiotics ever were found to be positively related only to asthma-associated AE, whereas the effect of LRTI on AE without asthma had an opposite effect. Levels of beta(1-->3)-glucans in mattress dust were inversely related to a doctor's diagnosis of asthma-associated AE [aOR = 0.75 (0.57-0.98)], and endotoxin levels to current symptoms of asthma-associated AE [aOR = 0.73 (0.57-0.94)].. The analyses of the PARSIFAL study revealed two different phenotypes of AE, depending on the association with asthma and wheezing ever. With regard to the hygiene hypothesis, help with haying, exposure to beta(1-->3)-glucans and endotoxin were found to be inversely associated with the AE phenotype associated with asthma and wheezing.

Topics: Adolescent; Agriculture; Asthma; beta-Glucans; Child; Child, Preschool; Cross-Sectional Studies; Dermatitis, Atopic; Dust; Endotoxins; Environmental Exposure; Female; Housing; Humans; Hypersensitivity, Immediate; Immunoglobulin E; Life Style; Male; Multivariate Analysis; Phenotype; Respiratory Sounds; Surveys and Questionnaires

Topics: Asthma; Bedding and Linens; beta-Glucans; Dust; Fungi; Humans

To inspect houses and analyze settled dust from 26 homes with asthmatic children in the Elsipogtog Reserve, New Brunswick, for contaminants known to be associated with respiratory symptoms. This pilot observational study was conducted in order to enable larger research into housing and health in Aboriginal communities.. Twenty-six homes were subject to an informed inspection and settled dust collection from the child's bedroom. The fine dust (< 300 microm) was analyzed for endotoxin, house dust mite and fungal glucan concentrations, as well as for building-associated fungi.. The percentage of homes in this study that had mould damage was slightly higher than in much larger studies in other parts of Canada. Qualitatively, the causes of the water and mould damage were similar to those found in a larger study in nearby PEI. However, in a few cases, the type of damage found in Elsipogtog was at a more advanced stage. House dust mite allergens, endotoxin and fungal glucan concentrations in settled dust included values that have been associated with increased respiratory symptoms. This selection of houses was, on average, cleaner than many homes studied in Canada. CONCLUSION. Although the range of mould damage observed in this study was similar to that seen elsewhere in Canada, the underlying causes tended to reflect more serious maintenance problems. A systematic evaluation of mould damage, on a community-wide basis, is a useful process to set priorities for repair.

Topics: Air Pollution, Indoor; Allergens; Animals; Asthma; beta-Glucans; Dust; Environmental Monitoring; Epidemiological Monitoring; Female; Housing; Humans; Indians, North American; Male; Maximum Tolerated Dose; Mites; New Brunswick; Pilot Projects; Severity of Illness Index

House dust samples collected for exposure studies are often stored for variable time periods until analysis. However, there is currently no information on the effects of dust storage on the content of biocontaminants. Therefore, associations were analysed between the levels of mite allergens (Der p 1, Der f 1), cat allergen (Fel d 1) and microbial components (endotoxin, beta(1-->3)-glucan) on the one hand and the storage duration of dust samples at -20 degrees C on the other hand.. Within the framework of a study on the influences of INdoor factors and Genetics on Asthma (INGA), dust samples were collected from living room floors between June 1995 and August 1998 and extracted according to a standardized protocol. The concentrations of Der p 1, Der f 1, Fel d 1 and beta(1-->3)-glucan were determined with specific enzyme immunoassays. Endotoxin content was quantified using a chromogenic kinetic Limulus amoebocyte lysate (LAL) test. All concentrations were expressed per gram of dust. Dust samples (n = 1236) were obtained from 655 homes in Hamburg, Hettstedt, Zerbst and Bitterfeld. Storage duration (range 8-298 days) was grouped into four categories ( 120 d). After adjustment for city of residence and season of dust sampling, means ratios comparing categories 2-4 to the first category were not statistically significant for Der p 1, Der f 1, endotoxin and beta(1-->3 glucan). However, Fel d 1 concentrations significantly declined with increased storage times of dust samples.. Storage of house dust at -20 degrees C for up to 10 months has no effect on mite allergen, endotoxin and beta(1-->3)-glucan levels. A potential loss of Fel d 1 during storage of frozen dust samples needs further investigations by repeated measurements of allergen in identical dust samples.

Topics: Air Pollution, Indoor; Allergens; Analysis of Variance; Animals; Antigens, Dermatophagoides; Arthropod Proteins; Asthma; beta-Glucans; Cysteine Endopeptidases; Dose-Response Relationship, Immunologic; Endotoxins; Germany; Glucans; Glycoproteins; Humans; Pyroglyphidae; Statistics as Topic; Time Factors

House dust-associated bacterial endotoxins have been shown to be associated with asthma severity, and a similar role has been suggested for fungal (1-->3)-beta-D-glucans. In this study the relation between these agents and peak expiratory flow (PEF) variability was investigated in 148 children 7 to 11 yr of age of whom 50% had self- or parent-reported chronic respiratory symptoms. All children self-monitored twice daily their PEF for a period of 16 wk. Dust samples were collected from mattresses and from living room and bedroom floors, and endotoxin and (1-->3)-beta-D-glucan were measured in dust extracts. The relations with mean daily PEF variability (Ampl%mean) were investigated by linear regression analysis, adjusting for dust mite allergen levels, presence of pets, and type of floor cover. In unadjusted analyses the levels of both endotoxin and (1--> 3)-beta-D-glucan per square meter of living room floor were significantly associated with PEF-variability (but not when expressed per gram of sampled dust), particularly in atopic children with asthma symptoms. Adjusted analyses showed the same association for (1--> 3)-beta-D-glucan but not for endotoxin. Although no associations were found with microbial agent levels in bedroom floor or mattress dust, high levels of (1-->3)-beta-D-glucan in living room floor dust apparently increase PEF variability in asthmatic children.

Topics: Air Pollution, Indoor; Asthma; beta-Glucans; Child; Dust; Endotoxins; Female; Glucans; Humans; Male; Peak Expiratory Flow Rate; Risk Factors