Exacerbation Of Allergic Asthma Research Articles

Lipopolysaccharide (LPS) exposure differently affects allergic asthma exacerbations and its amelioration by intranasal curcumin in mice

AimLipopolysaccharide (LPS) is ubiquitous in the environment and can therefore, exacerbate allergic responses. Studies have suggested immunoregulatory effects of LPS according to route, dose and stage of exposure. Present study has examined whether dose and stage of LPS exposure (during sensitization and challenge with OVA) exacerbates airway inflammations, antigen specific-IgE level, histamine release, Th1/Th2 cytokine response. Further, anti-asthmatic potential of curcumin, through intranasal route has been evaluated for the first time in LPS induced airway inflammation in an ovalbumin (OVA)-challenged mouse asthma model. MethodsBalb/c mice were first sensitized with OVA on 1st and 8th day and exposed to two LPS doses (0.1/1.0μg) separately on 2nd day and then further exposed to LPS with OVA-aerosol (from 9 to 14day). Further, lower LPS dose (0.1μg) was chosen for OVA exposed mouse model of asthma exacerbation study. Intranasal curcumin was administered from 9th to 14th day before every LPS exposure. ResultsExposure to LPS (0.1μg) exacerbates airway inflammations in terms of IgE level, Th2-cytokine response (IL-4 and IL-5), histamine release, EPO and MPO activities and oxidative stress. Intranasal curcumin has effectively ameliorated airway exacerbations whereas dexamethasone, a known glucocorticosteroid, was not promising as compared to intranasal curcumin. ConclusionSchedule and dose of LPS exposure determines asthma exacerbations and intranasal curcumin could be better immunomodulatory agent in LPS exposed asthma exacerbations.

The hyperinflammatory reactivity of post-asthma alveolar macrophages contributes to RSV-induced asthma exacerbations (HYP7P.269)

Abstract Respiratory syncytial virus (RSV) causes serious morbidity as a major etiological agent of allergic asthma exacerbations. We now report that mice that suffered a preceding allergic bronchial inflammation were more prone to develop severe inflammatory responses and AHR after RSV-infection. Post-asthma alveolar macrophages (AM), residing in the alveolar lumen after clearance of eosinophilia, were found to largely contribute to this RSV-induced inflammation exacerbation. This AM population exhibited increased proinflammatory cytokine secretion in response to RSV-challenge but failed to contribute to viral clearance. A selectively increased proinflammatory NF-κB p65 signaling along with unaltered antiviral type I IFN signaling and loss of viral phagocytic clearance appear to be at the basis of the post-asthma AM mediated inflammation exacerbation. Phenotypic analysis revealed that the majority of post-asthma AM consisted of immature SiglecFlowCD11blow/int cells. Full maturation of the immature SiglecFlowCD11blow/int post-asthma AM by intratracheal administration of GM-CSF was associated with a decrease in RSV-induced exacerbation parameters, including pulmonary inflammation and AHR. These results point to a cascade of events in which a prior allergic bronchial inflammation causes a maturation defect in post-asthma AM resulting in a hyperinflammatory reactivity of the cells to RSV-infection, which in turn contributes to the onset of RSV-induced asthma exacerbation.

Differential effects of particulate matter upwind and downwind of an urban freeway in an allergic mouse model.

Near-road exposure to air pollutants has been associated with decreased lung function and other adverse health effects in susceptible populations. This study was designed to investigate whether different types of near-road particulate matter (PM) contribute to exacerbation of allergic asthma. Samples of upwind and downwind coarse, fine, and ultrafine PM were collected using a wind direction-actuated ChemVol sampler at a single site 100 m from Interstate-96 in Detroit, MI during winter 2010/2011. Upwind PM was enriched in crustal and wood combustion sources while downwind PM was dominated by traffic sources. Control and ovalbumin (OVA)-sensitized BALB/cJ mice were exposed via oropharyngeal (OP) aspiration to 20 or 100 μg of each PM sample 2 h prior to OP challenge with OVA. In OVA-allergic mice, 100 μg of downwind coarse PM caused greater increases than downwind fine/ultrafine PM in bronchoalveolar lavage neutrophils, eosinophils, and lactate dehydrogenase. Upwind fine PM (100 μg) produced greater increases in neutrophils and eosinophils compared to other upwind size fractions. Cytokine (IL-5) levels in BAL fluid also increased markedly following 100 μg downwind coarse and downwind ultrafine PM exposures. These findings indicate coarse PM downwind and fine PM upwind of an interstate highway promote inflammation in allergic mice.

A Review of Spatial Variation of Allergenic Tree Pollen Within Cities

Urban trees provide a range of environmental and public health benefits. However, urban trees may also have an adverse effect on human health by increasing exposure to pollen. Many types of tree pollen are considered to be allergens and have been linked to various manifestations of allergic disease, including allergic sensitization, exacerbation of allergic rhinitis, and exacerbation of allergic asthma. An emerging body of literature suggests that the amount of pollen deposited annually varies widely over small spatial scales. While the health impacts of spatial variation in tree pollen within metropolitan areas could be large, the current literature has not been systematically reviewed. To fill this gap in knowledge, this review synthesizes existing evidence on how tree pollen is distributed on an intra-urban spatial scale. A better understanding of the spatial distribution of allergenic tree pollen within urban environments and its relation to health could inform increasingly common urban tree planting programs.

Phenotyping allergic rhinitis as early- or dual-phase responses using the environmental exposure unit

Allergic rhinitis (AR) is an IgE-mediated inflammatory condition of the nasal mucosa that results in sneezing, nasal congestion, and rhinorrhea at exposure to a particular allergen. Non-nasal symptoms include associated conjunctivitis, throat and palatal itch, and exacerbation of allergic asthma.1

Role of Interferon-λ in Allergic Asthma

Type III interferons (IFNs), or IFN-λ, are known to have potent antiviral and antiproliferative activities. It inhibits viral replication and upregulates cytotoxic responses to virally infected cells. Besides these characteristics, IFN-λ also has additional activities in the immune system. In fact, it induces the proliferation of Foxp3-expressing regulatory T cells mediated in part by dendritic cells and inhibit the production of IL-5 and IL-13 in vitro. Regulatory T cells and the Th2 cytokines like IL-5 and IL-13 play important roles in the pathogenesis of allergic asthma. In humans, there seems to be an inverse link between IFN-λ and the severity of allergic asthma and allergic asthma exacerbations. Asthmatic patients, without a detectable viral infection show an inverse correlation between IL-28 and IL-29 mRNA levels and severity of allergic responses in the airways. These additional features of IFN-λ that affect the adaptive immune system make it a potential immunotherapeutic agent for the treatment of allergic asthma.

IgE/antigen-mediated enhancement of IgE production is a mechanism underlying the exacerbation of airway inflammation and remodelling in mice.

IgE is known to enhance some antibody responses to specific antigens, but whether this contributes to allergic asthma remains unclear. We have previously found that repeated antigen challenges in mice sensitized with antigen-specific IgE monoclonal antibody (mAb) exacerbated airway inflammation and remodelling accompanied by increased levels of endogenous antigen-specific IgE and IgG1. Here, we investigated whether IgE/antigen-mediated enhancement of endogenous IgE production contributes to the exacerbation of airway inflammation and remodelling. BALB/c mice passively sensitized with ovalbumin (OVA) -specific IgE mAb were challenged with OVA intratracheally seven times; anti-IgE mAb was intraperitoneally administered 1 day before the fourth challenge. Treatment with anti-IgE mAb inhibited the increased level of endogenous OVA-specific IgE in serum, but not OVA-specific IgG1, and a biphasic increase in airway resistance at the fourth challenge. Furthermore, a biphasic increase in airway resistance, airway hyper-responsiveness to methacholine, OVA-specific IgE and IgG1 production, and infiltrations by neutrophils and eosinophils in the lungs at the seventh challenge were suppressed by treatment; airway remodelling, such as goblet cell hyperplasia and sub-epithelial fibrosis, was also reduced. In addition, the production of interleukin-17A, interleukin-33 and CXCL1 in the lungs related to these IgE-mediated responses was decreased by treatment. Collectively, we found that the mechanism leading to the exacerbation of allergic asthma is closely related to IgE/antigen-mediated enhancement of IgE production, suggesting that this may create a vicious circle leading to the chronic status in asthmatic patients having levels of antigen-specific IgE ready to form complexes with antigen.

Rhinovirus-induced IL-25 in asthma exacerbation drives type 2 immunity and allergic pulmonary inflammation.

Rhinoviruses (RVs), which are the most common cause of virally induced asthma exacerbations, account for much of the burden of asthma in terms of morbidity, mortality, and associated cost. Interleukin-25 (IL-25) activates type 2-driven inflammation and is therefore potentially important in virally induced asthma exacerbations. To investigate this, we examined whether RV-induced IL-25 could contribute to asthma exacerbations. RV-infected cultured asthmatic bronchial epithelial cells exhibited a heightened intrinsic capacity for IL-25 expression, which correlated with donor atopic status. In vivo human IL-25 expression was greater in asthmatics at baseline and during experimental RV infection. In addition, in mice, RV infection induced IL-25 expression and augmented allergen-induced IL-25. Blockade of the IL-25 receptor reduced many RV-induced exacerbation-specific responses including type 2 cytokine expression, mucus production, and recruitment of eosinophils, neutrophils, basophils, and T and non-T type 2 cells. Therefore, asthmatic epithelial cells have an increased intrinsic capacity for expression of a pro-type 2 cytokine in response to a viral infection, and IL-25 is a key mediator of RV-induced exacerbations of pulmonary inflammation.

The Involvement of Glucocorticoids in Psychological Stress-Induced Exacerbations of Experimental Allergic Asthma

Background: Psychological stress is associated with the aggravation of asthma symptoms. Glucocorticoids (GC), which are stress hormones released upon exposure to stress, have the potential to shift immune responses towards a predominant Th2 response by priming antigen-presenting cells to produce lower levels of IL-12 as well as reducing the development of regulatory T cells. However, the involvement of GC in psychological stress-induced exacerbations of allergic asthma has not yet been clarified. Methods: Sensitized mice were exposed to restraint stress followed by forced swimming stress, during which a GC receptor antagonist or a GC synthesis inhibitor was administered, and then antigen was inhaled. Corticosterone levels in the blood were measured in stressed and nonstressed mice. After antigen inhalation, the airway responses to aerosolized methacholine, epithelial mucus secretion and airway inflammation were evaluated, and the IL-13 contents in bronchoalveolar lavage fluid were measured. Results: The exposure to stress significantly increased corticosterone levels. Allergic airway responses and the increase of IL-13 contents evoked by antigen inhalation were significantly higher in stressed mice than in nonstressed mice. The administration of a GC receptor antagonist and a GC synthesis inhibitor during stress exposure significantly reduced the exacerbation of the airway responses and the increase of IL-13 contents in stressed mice challenged with antigen. Conclusions: These results indicate that the increased release of GC upon exposure to stress has a priming effect on the aggravation of allergic airway responses following the exposure, suggesting a pathophysiological role for the neuroendocrine axis in linking psychological stress to asthma exacerbations.

CCL17 Production by Dendritic Cells Is Required for NOD1-mediated Exacerbation of Allergic Asthma

Pattern recognition receptors are attractive targets for vaccine adjuvants, and polymorphisms of the innate receptor NOD1 have been associated with allergic asthma. To elucidate whether NOD1 agonist may favor allergic asthma in humans through activation of dendritic cells, and to evaluate the mechanisms involved using an in vivo model. NOD1-primed dendritic cells from allergic and nonallergic donors were characterized in vitro on their phenotype, cytokine secretion, and Th2 polarizing ability. The in vivo relevance was examined in experimental allergic asthma, and the mechanisms were assessed using transfer of NOD1-conditioned dendritic cells from wild-type or CCL17-deficient mice. NOD1 priming of human dendritic cells promoted a Th2 polarization profile that involved the production of CCL17 and CCL22 in nonallergic subjects but only CCL17 in allergic patients, without requiring allergen costimulation. Moreover, NOD1-primed dendritic cells from allergic donors exhibited enhanced maturation that led to abnormal CCL22 and IL-10 secretion compared with nonallergic donors. In mice, systemic NOD1 ligation exacerbated allergen-induced experimental asthma by amplifying CCL17-mediated Th2 responses in the lung. NOD1-mediated sensitization of purified murine dendritic cells enhanced production of CCL17 and CCL22, but not of thymic stromal lymphopoietin and IL-33, in vitro. Consistently, adoptive transfer of NOD1-conditioned dendritic cells exacerbated the Th2 pulmonary response in a CCL17-dependent manner in vivo. Data from this study unveil a deleterious role of NOD1 in allergic asthma through direct induction of CCL17 by dendritic cells, arguing for a need to address vaccine formulation safety issues related to allergy.

Application of vitamin E to antagonize SWCNTs-induced exacerbation of allergic asthma

The aggravating effects of zero-dimensional, particle-shaped nanomaterials on allergic asthma have been previously investigated, but similar possible effects of one-dimensional shaped nanomaterials have not been reported. More importantly, there are no available means to counteract the adverse nanomaterial effects to allow for their safe use. In this study, an ovalbumin (OVA)-sensitized rat asthma model was established to investigate whether single walled carbon nanotubes (SWCNTs) aggravate allergic asthma. The results showed that SWCNTs in rats exacerbated OVA-induced allergic asthma and that this exacerbation was counteracted by concurrent administration vitamin E. A mechanism involving the elimination of reactive oxygen species, downregulation of Th2 responses, reduced Ig production, and the relief of allergic asthma symptoms was proposed to explain the antagonistic effects of vitamin E. This work could provide a universal strategy to effectively protect people with allergic asthma from SWCNTs or similar nanomaterial-induced aggravating effects.

Resolvin E1 promotes resolution of inflammation in a mouse model of an acute exacerbation of allergic asthma

Endogenous mediators, such as RvE1 (resolvin E1), promote resolution of an inflammatory response and have potential as novel therapeutic agents. In the present study, we investigated the activity of RvE1 in a model of an acute exacerbation of chronic allergic asthma in mice. Animals sensitized to OVA (ovalbumin) received controlled low-level challenge with aerosolized antigen for 4 weeks, followed by a single moderate-level challenge to simulate an allergen-induced exacerbation of asthmatic inflammation. Induction of an exacerbation was associated with rapid recruitment of neutrophils, lymphocytes and eosinophils, together with increased levels of Th2 and pro-inflammatory cytokines. When administered before the final moderate-level challenge, RvE1 had only a modest effect on airway inflammation. To assess its effects when administered after induction of an exacerbation, we first characterized the cellular and molecular events associated with spontaneous resolution of airway inflammation over the following 96 h. Subsequently, we showed that administration of RvE1 at 2 and 8 h after the final challenge accelerated this process significantly. Specifically, RvE1 promoted a decline in the number of inflammatory cells, concentration of cytokines in lavage fluid and expression of mRNA for cytokines by macrophages, confirming its pro-resolution activity. In vitro, RvE1 had no apparent effect on lymphocytes, but suppressed significantly cytokine production by pulmonary macrophages, with evidence of down-regulation of the nuclear translocation of NF-κB (nuclear factor κB) p65 in these cells. The present study provides novel evidence that RvE1 can facilitate resolution of airway inflammation in a clinically relevant model of an acute exacerbation of asthma, possibly via its effects on activated pulmonary macrophages.

Role Of Interleukine-33 In Rhinovirus-Induced Allergic Asthma Exacerbation

Role Of Interleukine-33 In Rhinovirus-Induced Allergic Asthma Exacerbation

Diesel exhaust particle induction of IL-17A contributes to severe asthma

IL-17A has been implicated in severe forms of asthma. However, the factors that promote IL-17A production during the pathogenesis of severe asthma remain undefined. Diesel exhaust particles (DEPs) are a major component of traffic-related air pollution and are implicated in asthma pathogenesis and exacerbation. We sought to determine the mechanism by which DEP exposure affects asthma severity using human and mouse studies. BALB/c mice were challenged with DEPs with or without house dust mite (HDM) extract. Airway inflammation and function, bronchoalveolar lavage fluid cytokine levels, and flow cytometry of lung T cells were assessed. The effect of DEP exposure on the frequency of asthma symptoms and serum cytokine levels was determined in children with allergic asthma. In mice exposure to DEPs alone did not induce asthma. DEP and HDM coexposure markedly enhanced airway hyperresponsiveness compared with HDM exposure alone and generated a mixed T(H)2 and T(H)17 response, including IL-13(+)IL-17A(+) double-producing T cells. IL-17A neutralization prevented DEP-induced exacerbation of airway hyperresponsiveness. Among 235 high DEP-exposed children with allergic asthma, 32.2% had more frequent asthma symptoms over a 12-month period compared with only 14.2% in the low DEP-exposed group (P = .002). Additionally, high DEP-exposed children with allergic asthma had nearly 6 times higher serum IL-17A levels compared with low DEP-exposed children. Expansion of T(H)17 cells contributes to DEP-mediated exacerbation of allergic asthma. Neutralization of IL-17A might be a useful potential therapeutic strategy to counteract the asthma-promoting effects of traffic-related air pollution, especially in highly exposed patients with severe allergic asthma.

Serum amyloid A inhibits dendritic cell apoptosis to induce glucocorticoid resistance in CD4+ T cells

Mediators produced by the airway epithelium control the activation, recruitment, and survival of pulmonary dendritic cells (DC) that present antigen to CD4+ T cells during the genesis and exacerbation of allergic asthma. The epithelial-derived acute phase protein, serum amyloid A (SAA), induces DC maturation and TH17 polarization. TH17 responses are associated with severe forms of allergic asthma that are poorly controlled by corticosteroids. We sought to determine whether SAA would enhance the survival of DC during serum starvation and could then contribute to the development of a glucocorticoid-resistant phenotype in CD4+ T cells. Bone marrow-derived dendritic cells (BMDC) that were serum starved in the presence of SAA were protected from activation of caspase-3 and released less lactate dehydrogenase. In comparison with untreated serum-starved BMDC, treatment with SAA downregulated mRNA expression of the pro-apoptotic molecule Bim, increased production of the pro-survival heat shock protein 70 (HSP70), and induced secretion of pro-inflammatory cytokines. SAA-treated BMDC that were serum starved for 48 h remained capable of presenting antigen and induced OTII CD4+ T cells to secrete IL-17A, IL-17F, IL-21, IL-22, and IFNγ in the presence of ovalbumin. IL-17A, IL-17F, IL-21, and IFNγ production occurred even when the CD4+ T cells were treated with dexamethasone (Dex), whereas glucocorticoid treatment abolished cytokine secretion by T cells cocultured with untreated serum-starved BMDC. Measurement of Dex-responsive gene expression demonstrated CD4+ T cells as the target of glucocorticoid hyperresponsiveness manifest as a consequence of BMDC stimulation by SAA. Finally, allergic airway disease induced by SAA and antigen inhalation was unresponsive to Dex treatment. Our results indicate that apo-SAA affects DC to both prolong their viability and increase their inflammatory potential under apoptosis-inducing conditions. These findings reveal mechanisms through which SAA enhances the CD4+ T-cell-stimulating capacity of antigen-presenting cells that may actively participate in the pathogenicity of glucocorticoid-resistant lung disease.

Innate imprinting of resident alveolar macrophages in RSV-induced allergic asthma exacerbations (P6003)

Abstract Acute RSV-infections are seen as instigators of exacerbations in allergic asthma patients. The question which cells and/or molecules that orchestrate viral-induced asthma exacerbations remains unanswered. We now show that the innate (antiviral) functionality of post-asthma resident alveolar macrophages (rAM), present after the clearance of the allergic bronchial inflammation, is imprinted by this preceding allergic inflammation. In contrast to naïve rAM, post-asthma rAM exhibited strong proinflammatory reactivity during RSV-infection which significantly contributed to the increased global pulmonary inflammation observed in RSV-infected post-asthma mice. The strong proinflammatory reactivity of post-asthma rAM was mainly due to increased NF-κB p65 activation in these cells upon RSV-infection. Furthermore, compared to naïve rAM, post-asthma rAM displayed no direct contribution to virus clearance. In fact, post-asthma rAM did not show efficient uptake of the virus. Finally, compared to naïve rAM, the basal activation state of post-asthma rAM was found to be strongly skewed towards an M2-phenotype. Consequently, the polarized M2-activation status of post-asthma rAM can serve as a possible explanation for the aberrant antiviral innate responses of these cells. Together, innate imprinting of rAM by a preceding allergic inflammation strongly impairs RSV-antiviral responses of the post-asthma lungs and can therefore contribute to the onset of asthma exacerbations.

Membrane Cholesterol Removal from Human Eosinophils Disrupts Cholesterol Rich Membrane Microdomains Resulting in Down Regulated MAP Kinase Signaling but not JAK/STAT Signaling

Eosinophils contribute to allergic asthma exacerbation and can undergo excessive recruitment to the lungs where their activation leads to tissue damage and fibrosis. Interleukin-5 (IL-5) family cytokine receptors, which are critical for eosinophil recruitment/activation, are proposed to exist in membrane microdomains. Because cholesterol-rich microdomains are linked to signal regulation in diverse receptor systems, and because hypercholesterolemia is an asthma risk-factor, we tested the hypothesis that cholesterol-rich plasma membrane microdomains are central to IL-5-family cytokine action in eosinophils.

Allergens in Household Dust and Serological Indicators of Atopy and Sensitization in Detroit Children with History-Based Evidence of Asthma

Background. Home exposure to allergens is an important factor in the development of sensitization and subsequent exacerbations of allergic asthma. We investigated linkages among allergen exposure, immunological measurements, and asthma by examining (1) reservoir dust allergen levels in homes, (2) associations between presence of allergens in homes and sensitization status of resident children, and (3) associations between asthma status and total IgE, atopy (by Phadiatop), and positive allergen-specific tests. Methods. The study protocol was approved by Institutional Review Boards (IRBs) of the University of North Carolina Chapel Hill; Westat, Inc.; and the US Environmental Protection Agency Human Research Protocol Office. Data were collected from questionnaires, serum analyses, and household vacuum dust. Children (n = 205) were predominately African American (AA) (85.4%) and 51.6% were asthmatic. Sera from 185 children and home dust samples (n = 141) were analyzed for total and specific IgE antibodies to allergens from cat and dog dander, cockroach, dust mites, mice, rats, and molds. Results. Sixty percent of the homes had detectable levels of three or more dust allergens. The proportions of children with positive allergen-specific IgE tests were dust mite (32%), dog (28%), cat (23%), cockroach (18%), mouse (5%), rat (4%), and molds (24–36%). Children testing positive to a single allergen also had positive responses to other allergens. Those children with positive serum tests for cat, dog, and dust mite lived in homes with detectable levels of cat (51%), dog (90%), and dust mite (Der f 1) (92%) allergens. Correlations between children’s specific IgE levels and dust levels were linearly related for dog (p < .04), but not for cat (p = .12) or dust mite (Der f 1) (p = .21). Odds ratios (95% CI) for the associations between asthma and serum-specific IgE were over 1.0 for cat, dog, dust mite (Der f 1), cockroach, and four types of molds. House dust allergen exposure levels, however, exhibited no differences between asthmatic and non-asthmatic homes. Conclusions. Both the co-occurrence of multiple allergens in dust and the high frequency of multiple allergen sensitizations indicate that a broad-based intervention aimed at reducing multiple allergens (pets, pests, and molds) would be more successful than any approach that aimed at reducing one type of allergen.

CD4+CD25high Treg cells in peripheral blood during remission and exacerbation of allergic asthma in children

To determine the percentage of CD4+CD25(high) Treg cells in peripheral bloodCD4+ T cells of allergic asthmatic children during disease remission and exacerbation. Peripheral blood mononuclear cells (PBMC) and serum samples were collected from 6- to 11-year-old children with mild-to-moderate allergic asthma (n = 34)and from healthy controls (n = 15). CD4+CD25(high) T cells in PBMC were detected by flow cytometry. Total and specific IgE in serum were analysed by enzyme-amplified chemiluminescence, and IL-2 was measured by ELISA. There was no significant difference in CD4+CD25(high) T-cell proportions between asthmatic children in exacerbation and remission as compared with controls.CD4+CD25(high) T-cell percentages were not correlated with total and specific IgE. IL-2 was elevated in both disease remission and exacerbation but did not correlate significantly with CD4+CD25(high) T-cell percentages. CD4+CD25(high) T-cell proportion in the peripheral blood of total CD4+T cells is not reduced in children with allergic IgE-mediated asthma and does not differ between disease remission and exacerbation.

Particulate allergens potentiate allergic asthma in mice through sustained IgE-mediated mast cell activation.

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.