Document Detail


Particulate allergens potentiate allergic asthma in mice through sustained IgE-mediated mast cell activation.
MedLine Citation:
PMID:  21285515     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Cong Jin; Christopher P Shelburne; Guojie Li; Erin N Potts; Kristina J Riebe; Gregory D Sempowski; W Michael Foster; Soman N Abraham
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  121     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-04-07     Completed Date:  2011-04-27     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  941-55     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Air Pollutants
Allergens / chemistry*
Animals
Antigens, CD / biosynthesis
Antigens, CD63
Asthma / metabolism*
Bronchial Hyperreactivity / immunology*
Disease Models, Animal
Endocytosis
Gene Expression Regulation*
Hypersensitivity / metabolism*
Immunoglobulin E / metabolism*
Inflammation
Lipids / chemistry
Male
Mast Cells / cytology*
Membrane Microdomains
Mice
Mice, Inbred C57BL
Platelet Membrane Glycoproteins / biosynthesis
Grant Support
ID/Acronym/Agency:
AI056101/AI/NIAID NIH HHS; AI074751/AI/NIAID NIH HHS; AI081672/AI/NIAID NIH HHS; AI150021/AI/NIAID NIH HHS; DK050814/DK/NIDDK NIH HHS; DK077159/DK/NIDDK NIH HHS; DK077307/DK/NIDDK NIH HHS; ES016347/ES/NIEHS NIH HHS; P30-AI051445/AI/NIAID NIH HHS; R01 DK077159/DK/NIDDK NIH HHS; U54-AI057157/AI/NIAID NIH HHS; UC6-AI058607/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Air Pollutants; 0/Allergens; 0/Antigens, CD; 0/Antigens, CD63; 0/Cd63 protein, mouse; 0/Lipids; 0/Platelet Membrane Glycoproteins; 37341-29-0/Immunoglobulin E
Comments/Corrections

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