Caveolar transport through nasal epithelium of birch pollen allergen Bet v 1 in allergic patients Sakari Joenväärä, BS, Pirkko Mattila, PhD, Jutta Renkonen,

Slides:

Advertisements

Similar presentations

Are leukocytes in asthmatic patients aging faster

Advertisements

MicroRNA signature in patients with eosinophilic esophagitis, reversibility with glucocorticoids, and assessment as disease biomarkers Thomas X. Lu,

Repeated low-dose intradermal allergen injection suppresses allergen-induced cutaneous late responses Giuseppina Rotiroti, MD, Mohamed Shamji, PhD, Stephen.

Joseph A. Odhiambo, MMed, Hywel C. Williams, PhD, Tadd O

Striking deposition of toxic eosinophil major basic protein in mucus: Implications for chronic rhinosinusitis Jens U. Ponikau, MD, David A. Sherris,

Mauro Maniscalco, MD, PhD, Debora Paris, PhD, Dominique J

Asthma inflammatory phenotypes show differential microRNA expression in sputum Tania Maes, PhD, Francisco Avila Cobos, MSc, Florence Schleich, MD, PhD,

Airway epithelial cells in asthma

Increased TGF-β2 in severe asthma with eosinophilia

Epithelial proteome profiling suggests the essential role of interferon-inducible proteins in patients with allergic rhinitis Joseph Ndika, PhD, Liisa.

Calcitonin gene-related peptide– and vascular endothelial growth factor–positive inflammatory cells in late-phase allergic skin reactions in atopic subjects

Distinct TLR-mediated pathways regulate house dust mite–induced allergic disease in the upper and lower airways Ji-Hwan Ryu, PhD, Jung-Yeon Yoo, BS,

MicroRNA signature in patients with eosinophilic esophagitis, reversibility with glucocorticoids, and assessment as disease biomarkers Thomas X. Lu,

Histologic eosinophilic gastritis is a systemic disorder associated with blood and extragastric eosinophilia, TH2 immunity, and a unique gastric transcriptome

Assessing basophil activation by using flow cytometry and mass cytometry in blood stored 24 hours before analysis Kaori Mukai, PhD, Nicolas Gaudenzio,

Defective killing of Staphylococcus aureus in atopic dermatitis is associated with reduced mobilization of human β-defensin-3 Kevin O. Kisich, PhD, Charles.

Persistence of the IgE repertoire in birch pollen allergy

Selective dysfunction of p53 for mitochondrial biogenesis induces cellular proliferation in bronchial smooth muscle from asthmatic patients Thomas Trian,

Birch pollen immunotherapy results in long-term loss of Bet v 1–specific TH2 responses, transient TR1 activation, and synthesis of IgE-blocking antibodies

Is 9 more than 2 also in allergic airway inflammation?

Rapid and comprehensive discovery of unreported shellfish allergens using large-scale transcriptomic and proteomic resources Roni Nugraha, MSc, Sandip.

Genetic and histologic evidence for autophagy in asthma pathogenesis

Caveolar transport through nasal epithelium of birch pollen allergen Bet v 1 in allergic patients Sakari Joenväärä, BS, Pirkko Mattila, PhD, Jutta Renkonen,

Airway smooth muscle remodeling is a dynamic process in severe long-standing asthma Muhannad Hassan, MD, Taisuke Jo, MD, PhD, Paul-André Risse, PhD,

A critical role for IL-18 in transformation and maturation of naive eosinophils to pathogenic eosinophils Sathisha Upparahalli Venkateshaiah, PhD, Akanksha.

Ζ Chain–associated protein of 70 kDa (ZAP70) deficiency in human subjects is associated with abnormalities of thymic stromal cells: Implications for T-cell.

Role of p63/p73 in epithelial remodeling and their response to steroid treatment in nasal polyposis Chun Wei Li, PhD, Li Shi, MD, Ke Ke Zhang, MD, Tian.

IL-13 desensitizes β2-adrenergic receptors in human airway epithelial cells through a 15-lipoxygenase/G protein receptor kinase 2 mechanism Giusy D.

Small RNA profiling reveals deregulated phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/Akt pathway in bronchial smooth muscle.

Comparative transcriptomic analyses of atopic dermatitis and psoriasis reveal shared neutrophilic inflammation David F. Choy, BS, Daniel K. Hsu, PhD,

The National Biome Initiative: An allergy perspective

Airway epithelial cells from asthmatic children differentially express proremodeling factors Jesus M. Lopez-Guisa, PhD, Claire Powers, BA, Daniele File,

Merritt L. Fajt, MD, Stacy L

A network-based analysis of the late-phase reaction of the skin

Naturally processed T cell–activating peptides of the major birch pollen allergen Sonja Mutschlechner, PhD, Matthias Egger, PhD, Peter Briza, PhD, Michael.

Joseph A. Odhiambo, MMed, Hywel C. Williams, PhD, Tadd O

Minimally invasive skin tape strip RNA sequencing identifies novel characteristics of the type 2–high atopic dermatitis disease endotype Nathan Dyjack,

David D. Tieu, MD, Anju T. Peters, MD, Roderick T

Airway smooth muscle remodeling is a dynamic process in severe long-standing asthma Muhannad Hassan, MD, Taisuke Jo, MD, PhD, Paul-André Risse, PhD,

Eosinophil production of prostaglandin D2 in patients with aspirin-exacerbated respiratory disease Xin Feng, MD, Madison K. Ramsden, BS, Julie Negri,

Are leukocytes in asthmatic patients aging faster

CC chemokine receptors CCR1 and CCR4 are expressed on airway mast cells in allergic asthma Kawa Amin, PhD, Christer Janson, MD, PhD, Ilkka Harvima, MD,

Altered metabolic profile in patients with IgE to galactose-alpha-1,3-galactose following in vivo food challenge John W. Steinke, PhD, Shawna L. Pochan,

Weiguo Chen, PhD, Gurjit K. Khurana Hershey, MD, PhD

Intracellular residency of Staphylococcus aureus within mast cells in nasal polyps: A novel observation Stephen M. Hayes, MRCS, Robert Howlin, PhD, David.

Novel allergic asthma model demonstrates ST2-dependent dendritic cell targeting by cypress pollen Lucia Gabriele, BS, Giovanna Schiavoni, BS, Fabrizio.

Zheng Liu, MD, Jean Kim, MD, PhD, Joseph P

Cockroach allergens: Coping with challenging complexity

Basophil and eosinophil accumulation and mast cell degranulation in the nasal mucosa of patients with hay fever after local allergen provocation Alex.

CD23 surface density on B cells is associated with IgE levels and determines IgE- facilitated allergen uptake, as well as activation of allergen-specific.

Eosinophil production of prostaglandin D2 in patients with aspirin-exacerbated respiratory disease Xin Feng, MD, Madison K. Ramsden, BS, Julie Negri,

The gastrointestinal tract is critical to the pathogenesis of acute HIV-1 infection Saurabh Mehandru, MD, Klara Tenner-Racz, MD, Paul Racz, MD, PhD, Martin.

Risk of oral food challenges

Anti–IL-5 therapy reduces mast cell and IL-9 cell numbers in pediatric patients with eosinophilic esophagitis Iris M. Otani, MD, Arjun A. Anilkumar,

Expression of chemokines and chemokine receptors in lesional and nonlesional upper skin of patients with atopic dermatitis Eva Gros, MSc, Caroline Bussmann,

CCL17/thymus and activation-regulated chemokine induces calcitonin gene–related peptide in human airway epithelial cells through CCR4 Kandace Bonner,

An intranasal Syk-kinase inhibitor (R112) improves the symptoms of seasonal allergic rhinitis in a park environment Eli O. Meltzer, MD, Robert B. Berkowitz,

Alvaro A. Cruz, MD, Robert M

Monocyte chemotactic proteins in allergen-induced inflammation in the nasal mucosa: Effect of topical corticosteroids Pota Christodoulopoulos, BSca,

Eosinophil and neutrophil extracellular DNA traps in human allergic asthmatic airways Ryszard Dworski, MD, PhD, Hans-Uwe Simon, MD, PhD, Aimee Hoskins,

IL-9 and c-Kit+ mast cells in allergic rhinitis during seasonal allergen exposure: Effect of immunotherapy Kayhan T. Nouri-Aria, PhD, FRCPath, Charles.

Cure of HIV infection: Is the long wait over?

Alex KleinJan, PhD, Monique Willart, BSc, Leonie S

An ex vivo model of severe asthma using reconstituted human bronchial epithelium Delphine Gras, PhD, Arnaud Bourdin, MD, PhD, Isabelle Vachier, PhD, Laure.

Dendritic cells in nasal mucosa of subjects with different allergic sensitizations Susanne M. Reinartz, MD, Joost van Tongeren, MD, Danielle van Egmond,

Transcription factors in allergic diseases

An intranasal Syk-kinase inhibitor (R112) improves the symptoms of seasonal allergic rhinitis in a park environment Eli O. Meltzer, MD, Robert B. Berkowitz,

CCL17/thymus and activation-regulated chemokine induces calcitonin gene–related peptide in human airway epithelial cells through CCR4 Kandace Bonner,

Aarti Shikotra, BSc, David F. Choy, BSc, Chandra M

Chitinases and chitinase-like proteins in TH2 inflammation and asthma

Presentation transcript:

Caveolar transport through nasal epithelium of birch pollen allergen Bet v 1 in allergic patients Sakari Joenväärä, BS, Pirkko Mattila, PhD, Jutta Renkonen, DDS, Antti Mäkitie, MD, Sanna Toppila-Salmi, MD, Mikko Lehtonen, MD, Paula Salmi, BS, Satu Lehti, BS, Jarno Mäkinen, MTech, Raija Sormunen, PhD, Timo Paavonen, MD, Risto Renkonen, MD Journal of Allergy and Clinical Immunology Volume 124, Issue 1, Pages 135-142.e21 (July 2009) DOI: 10.1016/j.jaci.2008.11.048 Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Nasal epithelial cells and tissues were sampled from patients with birch pollen allergy and healthy subjects during the symptom-free winter period, before the intranasal pollen challenge, and 10 minutes after perturbation. The same subjects were sampled during the spring birch pollen season, when allergic individuals had symptoms. Three datasets were generated: Bet v 1 location and quantity (microscopy), Bet v 1–associated epithelial proteins (mass spectrometry), and epithelial transcriptomics. Journal of Allergy and Clinical Immunology 2009 124, 135-142.e21DOI: (10.1016/j.jaci.2008.11.048) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 A, Nasal epithelium from healthy subjects shows no Bet v 1 binding to the epithelium, whereas concanavalin A staining clearly indicated the epithelial lining in red (upper pair). One minute after the in vivo birch pollen challenge, there was a strong and patchy Bet v 1 clustering to the epithelium of allergic patients (lower pair, blue staining, white arrow; original magnification ×400). B, After 1 minute of nasal birch pollen challenge, most of the gold label in immuno-EM was on the epithelial surface (original magnification ×27,000). C, Often the clusters of Bet v 1 were located in the vicinity of desmosomes (original magnification ×18,000). D, Double immuno-EM showed coclustering of caveolin 2 (10 nm of gold) and Bet v 1 (5 nm of gold; arrows; original magnification ×10,000. E, Higher magnification of the area of the arrow in Fig 2, D (original magnification ×100,000. F, The clusters of Bet v 1 allergen were colocalized on the top of the cytoskeletal structures (arrows). G-I, Quantification of Bet v 1/mm2 (Fig 2, G) and Bet v 1 clusters/mm2 (Fig 2, H) and percentage of anti–Bet v 1 gold particles present in clusters within the nasal epithelium (Fig 2, I). Journal of Allergy and Clinical Immunology 2009 124, 135-142.e21DOI: (10.1016/j.jaci.2008.11.048) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 More than 500 individual photograph frames were taken from a nasal biopsy specimen from a challenged allergic patient (original magnification ×27,000), magnified, and collated to show the cross-section of the entire pseudostratified epithelium with underlying mast cells. A few high-magnification frames showing the anti–Bet v 1 gold particles and with arrows linking to the original positions within the tissue are shown. Journal of Allergy and Clinical Immunology 2009 124, 135-142.e21DOI: (10.1016/j.jaci.2008.11.048) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Nasal epithelial transcriptome analyses between healthy and allergic subjects. A, When specimens were compared, 94 and 85 transcripts were differentially expressed between the 2 groups during winter and spring, respectively. GO categories were enriched in pairwise combinations. B, Comparison between the nonchallenged (winter) and challenged (spring) specimens revealed great differences. There were many more transcripts with altered expression in healthy compared with allergic specimens. Journal of Allergy and Clinical Immunology 2009 124, 135-142.e21DOI: (10.1016/j.jaci.2008.11.048) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

A tiled EM micrograph of the normal pseudostratified epithelium for orientation when viewing Fig 3. Journal of Allergy and Clinical Immunology 2009 124, 135-142.e21DOI: (10.1016/j.jaci.2008.11.048) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

A comprehensive file of the pathway connecting 3 lists of data we had generated in this study from microscopy, mass spectrometry, and transcriptomics. Because this file contains 690 nodes and 113 edges, it is viewable only on a computer screen. Here 2 caveolar/lipid raft proteins, caveolin 2 and flotillin 2 (CAV2 and FLT2 from microscopy data), are connected to the Bet v 1–associated proteins GNDS, a Ras-related GTPase, and MYCBP2, an E3 ubiquitin-protein ligase, which carry out the proteasomal degradation of target proteins (both mass spectrometric data) and are linked to PTN4, a member of the cytoskeleton-binding proteins (found in transcriptome data). Journal of Allergy and Clinical Immunology 2009 124, 135-142.e21DOI: (10.1016/j.jaci.2008.11.048) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

The neighborhood of PTN4 and LIPL on the Medicel Integrator reference pathway displayed with Cytoscape. Red circle, Transcript; blue circles, protein; green circles, multimolecular complex from EBI database; small pink circles, interaction; yellow circle = metabolite, here glycerol, triacylglycerol (TGA) and fatty acid. Journal of Allergy and Clinical Immunology 2009 124, 135-142.e21DOI: (10.1016/j.jaci.2008.11.048) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

The neighborhood of 2 caveolar/lipid raft proteins, caveolin 1 and 2, on the Medicel Integrator reference pathway displayed with Cytoscape. Red circle, Transcript; blue circles, protein; green circle, multimolecular complex from the EBI database; small pink circles, interaction. Journal of Allergy and Clinical Immunology 2009 124, 135-142.e21DOI: (10.1016/j.jaci.2008.11.048) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions