Rapid systemic uptake of allergens through the respiratory mucosa
Available from: Claudia Traidl-Hoffmann
- "These data are consistent with the rapid allergen release and the weak localization of allergens in lysosomes observed in this study for the respiratory epithelial cell line A549. Transcytosis of allergens by respiratory epithelial cells may also explain higher serum concentrations of proteins after lower airway absorption than after nasal absorption observed in a mouse model (Hens et al., 2007). Allergens and non-allergenic proteins were also internalized by the bronchial epithelial cell lines NCI-H727 and Calu-3. "
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ABSTRACT: Epithelial cells of both the respiratory tract and the skin form a tight barrier against environmental harm. They represent the site of first contact for airborne allergen carriers. Consequently, in this study, we analyzed the uptake of grass pollen allergens by epithelial cells: Phl p 1 was selected as a glycosylated allergen containing disulfide bridges whereas Phl p 6 lacks post-translational modifications. Allergen uptake by the respiratory epithelial cell line A549 reached a plateau at 2 hours, and both allergens were localized intracellularly in non-acidic vesicles. In addition, in A549 cells allergens were exocytosed, suggesting a transcytosis mechanism in the passage of allergens over the respiratory epithelial barrier. In contrast, allergens were predominately localized in lysosomes in keratinocytes, and allergen uptake did not reach a plateau up to 24 hours. Notably, keratinocytes from atopic patients showed a significantly increased uptake of Phl p 1 as compared with healthy donors. Preincubation of epithelial cells with IL-4 and/or IFN-gamma to simulate inflammatory status led to an increased allergen uptake only in keratinocytes. This higher engulfment of allergens by inflammatory-type keratinocytes suggests a higher susceptibility of inflamed skin for the uptake of allergens and consequently a potentially higher risk for sensitization under natural exposure conditions, such as chronic atopic eczema.
Journal of Investigative Dermatology 03/2009; 129(8):1935-44. DOI:10.1038/jid.2008.459 · 7.22 Impact Factor
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ABSTRACT: The purpose of this review is to highlight important articles on upper airway diseases and immunotherapy that appeared in 2007. Advances in rhinitis include the realization that allergic rhinitis might be caused by local nasal IgE sensitization to aeroallergens in the absence of systemic evidence of IgE sensitization. After inhalation, allergens might reach systemic circulation. Epidemiologic studies continue to show that allergic rhinitis impairs school performance and is a risk factor for future asthma. New pathways are being identified in chronic sinusitis, as well as in different types of allergic ocular diseases. New treatments for patients with allergic rhinitis include use of beta-1,3-glucan, a mushroom product that can reduce allergic symptoms by inducing T(H)1 response, and olopatadine nasal spray. Studies on immunotherapy in 2007 suggest that sublingual immunotherapy induces similar immunologic alterations as those induced by subcutaneous immunotherapy, although to a lesser degree. Among allergists in the United States, there is a sizable variation in clinical practice, particularly related to concomitant administration of immunotherapy and beta-blockers, to administration of angiotensin-converting enzyme inhibitors, and to patients with HIV or autoimmune diseases. The combination of omalizumab with allergen subcutaneous immunotherapy can enhance clinical efficacy. Recombinant technology can modify allergen structure to prevent binding to IgE (allergenicity) while enhancing immunogenicity (stimulation of T cells), which might improve the safety and efficacy of immunotherapy.
The Journal of allergy and clinical immunology 10/2008; 122(3):481-7. DOI:10.1016/j.jaci.2008.06.027 · 11.48 Impact Factor
Available from: Gert-Jan Braunstahl
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ABSTRACT: Allergic asthma and rhinitis are manifestations of the atopic syndrome and often coexist. It has been demonstrated that allergic rhinitis is a strong risk factor for the onset of asthma in adults. Genetic and environmental factors are recognized as contributing factors to the development of the allergic airway syndrome. Insight in the risk factors responsible for allergic airways disease and the interaction between the involved organs results in a better understanding and treatment of the syndrome. Several mechanisms have been proposed for the interaction between upper and lower airways in allergic rhinitis and asthma. It has been clearly shown in many studies that impaired nasal function affects the lower airways of patients with asthma. The evidence for aspiration of nasal contents or neural reflexes as an explanation for nasobronchial cross-talk is lacking. To date, most human and animal data point toward a systemic pathway linking the upper and lower airways, involving both bloodstream and bone marrow. Serum IL-5 and blood eosinophils are increased as well as adhesion molecule expression after local allergen challenge. Moreover, mucosal inflammation was not restricted to the challenged organ only, but extended throughout the whole airway in subjects with allergic rhinitis. Nasobronchial interaction in allergic airway disease has profound impact on daily clinic. Nasal therapy in allergic rhinitis patients with asthma has a beneficial effect on asthma symptoms, bronchial hyperresponsiveness, and airway inflammation. Furthermore, it reduces the risk of asthma exacerbations. It stresses the importance of an integrated therapeutic approach involving both ends of the respiratory tract.
Proceedings of the American Thoracic Society 12/2009; 6(8):652-4. DOI:10.1513/pats.200906-052DP
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