Expression and immunolocalisation of antimicrobial peptides within human palatine tonsils
Epithelial Research Group, Institute for Cell & Molecular Biosciences, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK. The Journal of Laryngology & Otology
(Impact Factor: 0.67).
11/2007; 121(10):973-8. DOI: 10.1017/S0022215107006184
Background: Recurrent acute tonsillitis is one of the most frequent ENT referrals, yet its pathogenesis remains poorly understood, and tonsillectomy still costs the National Health Service more than £60 000 000 annually. Antimicrobial cationic peptides are components of the innate immune system. They are generally small, highly positively charged peptides with broad spectrum antimicrobial activity which function as the body's ‘natural antibiotics'. The role of antimicrobial cationic peptides in the susceptibility of patients to recurrent acute tonsillitis is unknown.
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- "In dry eye conditions, conjunctival and corneal impression cytology reveals elevated levels of LEAP-2 (Mohammed et al., 2011). Protein and gene expression of LEAP-2 are previously described in tonsillar tissue (Ball et al., 2007). "
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In the upper airway, the production of antimicrobial peptides (AMPs) protects against bacteria, viruses and fungi. Previous investigations have revealed downregulated expression of AMPs in different manifestations of allergic disease. In this study, we examined the expression of LL-37, RNase7 and LEAP-2 in tonsillar tissue and studied a possible relation to seasonal allergic rhinitis (SAR).Methods
Tonsils, obtained from patients with SAR and non-allergic controls, were examined for the occurrence of LL-37, Ribonuclease7 (RNase7) and Liver-expressed antimicrobial peptide 2 (LEAP-2) with real-time RT-PCR and immunohistochemistry. Tonsillar mononuclear cells were cultured in presence or absence of LEAP-2 or LL-37 and analyzed for cytokine levels using ELISA.ResultsmRNA and protein for LL-37, RNase 7 and LEAP-2 were found in all tonsils. Immunohistochemistry revealed prominent staining for LL-37 and RNase7 in the tonsillar epithelium, whereas a moderate staining was seen with LEAP-2. Real-time RT-PCR showed a downregulation of RNase7 and LEAP-2 in the allergic as compared to the non-allergic group. Mononuclear cells cultured in presence of LEAP-2 or LL-37 demonstrated reduced levels of IL-10.Conclusion
The present study demonstrates the presence and function of LEAP-2, LL-37 and RNase7 in tonsils. Moreover, a downregulation of LEAP-2 and RNase7 is seen in SAR patients, indicating that allergic individuals may be more susceptible to respiratory tract infections due to an impaired antimicrobial defense.This article is protected by copyright. All rights reserved.
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- "In the airways, the epithelium provides a barrier to entry of pathogens through tight junctions and mucociliary functions, but also through the production of antimicrobial peptides (AMPs) (Ball et al., 2007; Schwaab et al., 2009, 2010 Tieu et al., 2010). Their mechanisms of action include a variable degree of antimicrobial activity against bacteria, fungi, and some enveloped viruses (Bals et al., 1998). "
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ABSTRACT: Airway infections are known to cause exacerbations of allergy and asthma. Tonsils constitute a primary site for microbial recognition and triggering of the immune system in the airways. Human β-defensins (HBDs) are antimicrobial peptides with an important role in this defense. Our aim was to investigate HBD1-3 in tonsillar tissue and their potential role in allergic rhinitis (AR). Tonsils, obtained from patients with AR and non-allergic controls, and isolated tonsillar CD4(+), CD8(+) and CD19(+) lymphocytes were analyzed for HBD1-3 expression using real-time RT-PCR and/or immunohistochemistry. Tonsillar tissue, mixed tonsillar lymphocytes and airway epithelial cells (AECs) were cultured with or without IL-4, IL-5, IL-13 or histamine followed by measurements of HBD1-3 release using ELISA. HBD1-3 were present in tonsillar tissue, including epithelial, CD4(+), CD8(+) and CD19(+) cells. The expression was reduced in allergic compared to healthy tonsils. Stimulation of AECs with IL-4, IL-5 and histamine down-regulated the HBD release, whereas no effects were seen in cultured tonsils or lymphocytes. This study demonstrates presence of HBD1-3 in tonsils and that the levels are reduced in patients with AR. Together with the down-regulation of HBDs in epithelial cells in the presence of allergic mediators suggest that AR patients have an impaired antimicrobial defense that might make them more susceptible to respiratory tract infections.
Available from: Ragna Thorleifsdottir
- "Our data also contrast with those of Ball et al.  which is likely due to a difference in the antibody used and the methodology selected. We concluded that the antibody used herein is specific for LL-37, especially as this LL-37 staining was entirely blocked by overnight pre-incubation of the antibody with LL-37 peptide (Fig. 4g). "
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ABSTRACT: Antimicrobial peptides are essential elements of epithelial defense against invading micro-organisms. The palatine tonsils are positioned at the entry of the airway and the gut and as such are ideally situated to act as immune sentinels in the pharynx protecting against microbial invasion. Tonsils express a number of antimicrobial peptides including hCAP18/LL-37. Here we clearly define the expression of hCAP18/LL-37 in the tonsils showing unequivocally that hCAP18/LL-37 is mainly expressed by infiltrating neutrophils and follicular CD11c+CD13+HLA-DR+ dendritic cells, rarely by macrophages, and never by the epithelium itself. To explore possible functions for follicle-derived LL-37, we stimulated tonsil mononuclear cells with LL-37 in vitro and observed the secretion of the proinflammatory cytokines CCL5 and CXCL9, expression of IFN-γ and MX-1 and down-regulation of chemokine receptors CCR4 and CCR6 which are involved in tissue-selective T cell trafficking. Taken together, these data illustrate new potential immunoregulatory functions for hCAP18/LL-37 in the tonsils.
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