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  • 1
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background The dysfunction of the mucosal interface of the upper respiratory tract in cystic fibrosis (CF) patients is clinically visible by the development of nasal polyps (NP) at a young age. Innate defence markers and inflammatory mediators in NP from patients with CF were compared with non-cystic fibrosis nasal polyps (non-CF-NP) to determine a possible different immunological background in macroscopically similar tissue.Methods Surgical samples were obtained from patients with non-CF-NP, cystic fibrosis patients with nasal polyps (CF-NP) and control patients (CO). With real time PCR, the mRNA expression of human β defensins (HBD) 2 and 3, toll-like receptors (TLR) 2 and 4 and the macrophage mannose receptor (MMR) were measured. On homogenates of the surgical samples eotaxin, myeloperoxidase (MPO), IL-5 and IL-8 protein content was measured using commercial ELISA kits; IgE and eosinophilic cationic protein (ECP) were measured by the Unicap system.Results In CF-NP we found a statistically significant higher mRNA expression of HBD 2 compared with non-CF-NP and CO and of TLR 2 compared with non-CF-NP. In the non-CF-NP group, MMR mRNA expression was significantly elevated compared with CO and CF-NP. For TLR 4 mRNA expression no statistically significant differences were found between groups. IL-5 was below detection level in all CO and CF-NP, but was measurable in 80% of the non-CF-NP. MPO and IL-8 concentrations were significantly higher in CF-NP compared with CO and non-CF-NP, whereas ECP, eotaxin and IgE were significantly higher in the non-CF-NP group.Conclusions We here demonstrate that CF-NP and non-CF-NP not only differ in terms of inflammatory mediator profile, but also in terms of innate markers.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Bilateral nasal polyposis (NP) is characterized by high concentrations of IgE in NP tissue, which show no relation to the atopic status. We aimed to study the relationship between systemic and local IgE formation, nasal carriage of Staphylococcus aureus and nasal polyposis.Methods:  In serum and nasal tissue homogenates from 24 NP patients and 12 controls, we determined concentrations of total IgE and IgE antibodies to inhalant allergens and S. aureus enterotoxins (SAEs; A,B,C,D,E,TSST) by ImmunoCAP. Tissue cryosections were stained for CD3, CD20, CD38, CD23, FcεRI, IgE and SEA/SEB.Results:  We demonstrated a higher incidence of S. aureus colonization (17/24) and IgE antibodies to SAEs in NP tissue (12/24) compared with controls (3/12 and 0/12, respectively). Total IgE and IgE antibodies in serum and NP tissue were dissociated because of local polyclonal IgE formation in NP tissue. Staining of NP tissue revealed follicular structures characterized by B and T cells, and lymphoid accumulations with diffuse plasma cell infiltration.Conclusions:  We demonstrated the organization of secondary lymphoid tissue in polyp tissue and a polyclonal hyper-immunoglobulinemia E associated with the presence of IgE antibodies to SAEs, colonization with S. aureus, and tissue eosinophilia in a relevant subgroup of polyp patients.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: Alternative splicing of the interleukin-5 receptor alpha (IL-5Rα)-subunit leads to the generation of a signalling, membrane-anchored (TM) isoform, or a secreted [soluble (SOL)], antagonistic variant. Given the key role of IL-5 in eosinophil function, we investigated SOL IL-5Rα expression pattern in an eosinophil-associated disease such as nasal polyposis (NP).Methods: An SOL IL-5Rα enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction (PCR) were established and applied in serum, nasal secretion and nasal tissue of controls (n = 12), and NP patients (n = 42) with or without asthma.Results: Analysis of serum, nasal secretion, and nasal tissue samples revealed that SOL IL-5Rα protein concentrations were significantly increased in NP vs control tissue. Within the NP group, there was a significant up-regulation of SOL IL-5Rα in patients with systemic airway disease. These findings were confirmed at the mRNA level, using an optimized real-time reverse-transcriptase PCR procedure.Conclusions: This report demonstrates SOL IL-5Rα transcript and protein up-regulation in NP. Soluble IL-5Rα differentiates nasal polyps with or without concomitant asthma. As SOL IL-5Rα is strongly up-regulated for disease and has antagonistic properties in vitro, our studies shed new light on the mechanisms of specific immunomodulatory therapies, such as anti-IL-5.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Munksgaard International Publishers
    Allergy 59 (2004), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  The role of infectious agents in the onset and maintenance of chronic sinus disease is still not fully understood. Macrophage mannose receptor (MMR), an innate pattern recognizing receptor, capable of phagocytosis of invaders and signal transduction for proinflammatory mechanisms, might be of importance in immune interactions in chronic sinus disease.Objective:  We examined the MMR in sinonasal airway mucosa to evaluate its possible role in chronic rhinosinusitis (CS) and nasal polyposis (NPs).Methods:  Surgical samples from patients with sinonasal disease were investigated with real-time RT-PCR for quantification of MMR mRNA expression, and the presence and location of MMR-positive cells was analysed by immunohistochemistry.Results:  Quantification of MMR mRNA showed a statistically significant higher expression in NPs compared to CS without NP and controls. Immunohistochemistry revealed expression of MMR in all tissue samples; however, in NP we found an enhanced positive cellular staining including cell aggregates.Conclusions:  We could demonstrate for the first time that the expression of MMR is significantly upregulated in NP compared to patients with CS without NP or turbinate tissue of controls. Macrophages expressing MMR, accumulated in cell aggregates in NPs, play a possible key role in pathogen–macrophage interaction in NP disease.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Munksgaard International Publishers
    Allergy 58 (2003), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Measurement of innate markers in nasal mucosa, tonsils and adenoids might lead to new views about the role of innate immunity in the upper airway. In this study, the expression of human β-defensins (HBD) 2 and 3 and toll-like receptors (TLR) 2 and 4 in various upper airway diseases was investigated.Methods:  Surgical samples from patients with tonsillar disease (n = 18), hypertrophic adenoids (n = 10) and sinonasal disease (n = 30) (chronic sinusitis, nasal polyps, turbinate mucosa as controls) were investigated by immunohistochemistry. Quantification of HBD-2 and 3 mRNA, TLR-2 and 4 mRNA expression was performed by real-time polymerase chain reaction (PCR).Results:  Immunohistochemistry revealed a strong expression of HBD-2 in tonsillar tissue. Quantification of HBD-2 and HBD-3 mRNA showed a more than tenfold higher expression in tonsillar tissue than in adenoids, whereas in nasal biopsies, only negligible defensin expression could be measured. No significant differences were found for TLR-4 between the various tissues, whereas TLR-2 expression in adenoids was significantly lower compared with other tissues.Conclusion:  These results demonstrate a strong defensin expression in tonsillar tissue compared with nasal and paranasal mucosa and adenoids. Toll-like receptor expression in all these tissues illustrates a possibly important immunological sentinel function of upper airway mucosa.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Munksgaard International Publishers
    Allergy 57 (2002), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  This paper reports a study on the concentrations of the pro-inflammatory cytokines IL-18 and IL-1β in nasal secretions of allergic rhinitis patients in relation to ECP and nasal symptoms.Methods:  We measured IL-18 and IL-1β concentrations using ELISA, and eosinophilic cationic protein (ECP) using the CAP system, in nasal secretions of 15 seasonal allergic rhinitis (SAR) patients at six visits throughout the pollen season. Pollen exposure, nasal and ocular symptoms were monitored daily. Furthermore, we measured IL-18, IL-1β and ECP concentrations in nasal secretions of 19 controls and 20 symptomatic persistent allergic rhinitis (PAR) patients with house dust mite allergy.Results:  In SAR, the increase of IL-18, IL-1β and ECP paralleled the pollen flight with a time delay. IL-18 and IL-1β significantly increased during the pollen season compared to baseline, and differently from ECP, remained elevated until 4 weeks after the season. In PAR, the concentrations of IL-18 and ECP, but not IL-1β, were significantly higher compared to controls, with IL-18 concentrations also being significantly higher than in SAR.Conclusion:  This is the first study to demonstrate the up-regulation of IL-18 in nasal secretions in allergic rhinitis. The persistence of elevated IL-18 concentrations until after the season and the high concentrations in PAR compared to SAR suggests its role in persistent allergic inflammation.
    Type of Medium: Electronic Resource
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