Show simple item record

dc.contributor.advisor Abraham, Soman N en_US
dc.contributor.author Jin, C
dc.contributor.author Shelburne, CP
dc.contributor.author Li, G
dc.contributor.author Potts, EN
dc.contributor.author Riebe, KJ
dc.contributor.author Sempowski, GD
dc.contributor.author Foster, WM
dc.contributor.author Abraham, SN
dc.coverage.spatial United States
dc.date.accessioned 2010-05-10T19:55:23Z
dc.date.issued 2011-03
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/21285515
dc.identifier 43584
dc.identifier.citation J Clin Invest, 2011, 121 (3), pp. 941 - 955
dc.identifier.uri http://hdl.handle.net/10161/2358
dc.description Dissertation en_US
dc.description.abstract Allergic asthma is characterized by airway hyperresponsiveness, inflammation, and a cellular infiltrate dominated by eosinophils. Numerous epidemiological studies have related the exacerbation of allergic asthma with an increase in ambient inhalable particulate matter from air pollutants. This is because inhalable particles efficiently deliver airborne allergens deep into the airways, where they can aggravate allergic asthma symptoms. However, the cellular mechanisms by which inhalable particulate allergens (pAgs) potentiate asthmatic symptoms remain unknown, in part because most in vivo and in vitro studies exploring the pathogenesis of allergic asthma use soluble allergens (sAgs). Using a mouse model of allergic asthma, we found that, compared with their sAg counterparts, pAgs triggered markedly heightened airway hyperresponsiveness and pulmonary eosinophilia in allergen-sensitized mice. Mast cells (MCs) were implicated in this divergent response, as the differences in airway inflammatory responses provoked by the physical nature of the allergens were attenuated in MC-deficient mice. The pAgs were found to mediate MC-dependent responses by enhancing retention of pAg/IgE/FcεRI complexes within lipid raft–enriched, CD63(+) endocytic compartments, which prolonged IgE/FcεRI-initiated signaling and resulted in heightened cytokine responses. These results reveal how the physical attributes of allergens can co-opt MC endocytic circuitry and signaling responses to aggravate pathological responses of allergic asthma in mice.
dc.format.extent 941 - 955
dc.format.mimetype application/pdf
dc.language eng
dc.language.iso en_US
dc.relation.ispartof J Clin Invest
dc.relation.isversionof 10.1172/JCI43584
dc.subject Air Pollutants
dc.subject Allergens
dc.subject Animals
dc.subject Antigens, CD
dc.subject Antigens, CD63
dc.subject Asthma
dc.subject Bronchial Hyperreactivity
dc.subject Disease Models, Animal
dc.subject Endocytosis
dc.subject Gene Expression Regulation
dc.subject Hypersensitivity
dc.subject Immunoglobulin E
dc.subject Inflammation
dc.subject Lipids
dc.subject Male
dc.subject Mast Cells
dc.subject Membrane Microdomains
dc.subject Mice
dc.subject Mice, Inbred C57BL
dc.subject Platelet Membrane Glycoproteins
dc.title Particulate allergens potentiate allergic asthma in mice through sustained IgE-mediated mast cell activation.
dc.type Journal Article
dc.department Molecular Genetics and Microbiology en_US
duke.embargo.months 24 en_US
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/21285515
pubs.issue 3
pubs.organisational-group /Duke
pubs.organisational-group /Duke/Faculty
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Immunology
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Molecular Genetics and Microbiology
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine/Medicine, Duke Human Vaccine Institute
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Pathology
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Cancer Institute
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Human Vaccine Institute
pubs.publication-status Published
pubs.volume 121
dc.identifier.eissn 1558-8238

Files in this item

This item appears in the following Collection(s)

Show simple item record