Particulate allergens potentiate allergic asthma in mice through sustained IgE-mediated mast cell activation
Cong Jin, … , W. Michael Foster, Soman N. Abraham
Cong Jin, … , W. Michael Foster, Soman N. Abraham
Published February 1, 2011
Citation Information: J Clin Invest. 2011;121(3):941-955. https://doi.org/10.1172/JCI43584.
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Research Article Cell biology Immunology Inflammation Pulmonology

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 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, Kristina J. Riebe, Gregory D. Sempowski, W. Michael Foster, Soman N. Abraham

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Figure 2

MCs are required for pulmonary pathological responses to pAgs and sAgs in sensitized mice.

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MCs are required for pulmonary pathological responses to pAgs and sAgs i...
Pulmonary pathological responses in OVA/TNP-sensitized mice after exposure to soluble OVA/TNP (sAg) or particles conjugated with OVA/TNP (pAg). (A) AHR at 24 hours after challenge in WT (left) or mast cell–deficient (Wsh) mice (right). (B) BAL eosinophil counts and (C) lung histology in WT, Wsh, and BMMC-repleted Wsh mice were examined at 48 hours after the challenge. In panels B and C, for WT mice, n = 4, *P < 0.05, pAg vs. sAg; §P < 0.01, sAg vs. PBS; for BMMC-repleted Wsh mice: n = 4, **P < 0.05, pAg vs sAg; §§P < 0.01, sAg vs. PBS. Eosinophil responses to sAg or pAg in Wsh mice were largely attenuated than in WT mice or BMMCs repleted Wsh mice (n = 4, #P < 0.05). (D) H&E-stained lung tissue images in WT, Wsh, and BMMC-reconstituted Wsh mice show eosinophils accumulating around small bronchioles (B) and vasculature (V). Data are representative of samples from 4 mice. Scale bars: 25 μm.