Caveolar transport through allergen Bet v 1 in allergic nasal epithelium of birch pollen patients

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:124

Article

Joenvaara, Sakari^1,2,3  Mattila, Pirkko³  Renkonen, Jutta^1,2,4  Makitie, Antti⁵  Toppila-Salmi, Sanna^6,7  Lehtonen, Mikko^6,7  Salmi, Paula^1,2  Lehti, Satu^1,2  Makinen, Jarno³  Sormunen, Raija⁸  Paavonen, Timo⁹  Renkonen, Risto^1,2,4 

[1] Univ Helsinki, Haartman Inst, Transplantat Lab, FI-00014 Helsinki, Finland

[2] Univ Helsinki, Haartman Inst, Infect Biol Res Program, FI-00014 Helsinki, Finland

[3] Medicel Ltd, Helsinki, Finland

[4] Helsinki Univ Cent Hosp, HUSLAB, Helsinki, Finland

[5] Helsinki Univ Hosp, Dept Otolaryngol Head & Neck Surg, Helsinki, Finland

[6] Univ Tampere, FIN-33101 Tampere, Finland

[7] Tampere Univ Hosp, Dept Eye Ear & Oral Dis, Tampere, Finland

[8] Oulu Univ, Dept Pathol, Oulu, Finland

[9] Tampere Univ, Dept Pathol, FIN-33101 Tampere, Finland

关键词: Pollen;    allergy;    epithelium;    caveola;    lipid raft;    cytoskeleton;    systems biology;    pathway;    integration;   

DOI  :  10.1016/j.jaci.2008.11.048

来源: Elsevier

【 摘 要 】

Background: Previous work in type I pollen allergies has focused on aberrant immunoresponses. Objective: Our systems-level analyses explore the role of epithelium in early pathogenesis of type I allergic reactions. Methods: We began top-down analyses of differences in human nasal epithelial cells and biopsy specimens obtained from patients with birch allergy and healthy control subjects in the resting state and after intranasal in vivo birch pollen challenges. Immunohistochemistry, immunotransmission electron microscopy, mass spectrometry, transcriptomics, and integration of data to a pathway were conducted. Results: Bet v 1 allergen bound to epithelium immediately after in vivo birch pollen challenge during winter only in allergic individuals. It also travelled through epithelium with caveolae to mast cells. Sixteen unique proteins were found to bind to the Bet v I column only in lysates from allergic epithelial cells; 6 of these were caveolar and 6 were cytoskeletal proteins. The nasal epithelial transcriptome analysis from allergic and healthy subjects differed during the winter season, and these subjects also responded differentially to birch pollen challenge. Within this pollen-induced response, the gene ontology categories of cytoskeleton and actin cytoskeleton were decreased in allergic patients, whereas the actin-binding category was enriched in healthy subjects. Integration of microscopic, mass spectrometric, and transcriptomic data to a common protein-protein binding network showed how these were connected to each other. Conclusion: We propose a hypothesis of caveolae-dependent uptake and transport of birch pollen allergen in the epithelium of allergic patients only. Application of discovery-driven methodologies can provide new hypotheses worth further analysis of complex multifactorial diseases, such as type I allergy. (J Allergy Clin Immunol 2009;124:135-42.)

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