title: Particulate allergens potentiate allergic  asthma in mice through sustained  IgE-mediated mast cell activation.
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.
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27514, USA.
authors.forename: Cong
authors.initials: C
authors.lastname: Jin
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Shelburne
authors.forename: Guojie
authors.initials: G
authors.lastname: Li
authors.forename: Erin N
authors.initials: EN
authors.lastname: Potts
authors.forename: Kristina J
authors.initials: KJ
authors.lastname: Riebe
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Sempowski
authors.forename: W Michael
authors.initials: WM
authors.lastname: Foster
authors.forename: Soman N
authors.initials: SN
authors.lastname: Abraham
mesh_terms: D000393:Air Pollutants; D000485:Allergens / Q000737:chemistry*; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D001249:Asthma / Q000378:metabolism*; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D004195:Disease Models, Animal; D004705:Endocytosis; D005786:Gene Expression Regulation; D006967:Hypersensitivity / Q000378:metabolism*; D007073:Immunoglobulin E / Q000378:metabolism*; D007249:Inflammation; D008055:Lipids / Q000737:chemistry; D008297:Male; D008407:Mast Cells / Q000166:cytology*; D021962:Membrane Microdomains; D051379:Mice; D008810:Mice, Inbred C57BL; D010980:Platelet Membrane Glycoproteins / Q000096:biosynthesis; D060149:Tetraspanin 30
chemical_list: D000393:Air Pollutants; D000485:Allergens; D015703:Antigens, CD; C554587:Cd63 protein, mouse; D008055:Lipids; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; D007073:Immunoglobulin E