Caveolar transport through nasal epithelium of birch pollen allergen Bet v 1 in allergic patients - 15/08/11
, Pirkko Mattila, PhD b, , Jutta Renkonen, DDS a, c, , Antti Mäkitie, MD d, Sanna Toppila-Salmi, MD e, Mikko Lehtonen, MD e, Paula Salmi, BS a, Satu Lehti, BS a, Jarno Mäkinen, MTech b, Raija Sormunen, PhD f, Timo Paavonen, MD g, Risto Renkonen, MD a, c, ⁎ 
Reprint requests: Risto Renkonen, MD, Transplantation Laboratory, Haartman Institute, PO BOX 21 (Haartmaninkatu 3), FI-00014 University of Helsinki, Finland.Abstract |
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 1 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.
Le texte complet de cet article est disponible en PDF.Key words : Pollen, allergy, epithelium, caveola, lipid raft, cytoskeleton, systems biology, pathway, integration
Abbreviations used : EM, GO, Immuno-EM, NCBI
Plan
| Supported in part by Research Grants from the Academy of Finland, the Technology Development Centre (TEKES), the Sigrid Juselius Foundation, and Helsinki University Central Hospital Research Funds, Helsinki, Finland. |
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| Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest. |
Vol 124 - N° 1
P. 135 - juillet 2009 Retour au numéro
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