Inhaled aerosolized nicotine suppresses the lung eosinophilic response to house dust mite allergen

Nicotine of unprecedented concentrations and purity is being inhaled by those using commercially available electronic nicotine delivery systems (ENDS). The consequences of this route of self-administration on the immunological response to inhaled allergens are not known. In mice, sensitization and inhalation challenge with the common environmental house dust mite (HDM) allergen is an experimental model of this response. When mice were exposed to aerosolized nicotine base (aeroNic) twice daily, 5 days/wk for 8 wk, the HDM-induced recruitment of eosinophils (EOS) was substantially reduced as measured in bronchial alveolar lavage fluid (BALF). Oral nicotine administration had no effect. HDM challenge in the presence of nicotinic receptor subtype α7 (α7)-specific type-1 positive allosteric modulators (PAMs) was alone sufficient to suppress EOS. RNA analysis of alveolar macrophages (AM) collected from BALF after HDM challenge of aeroNic revealed that α7 activation strongly suppresses initiation of Ccl24 (eotaxin 2) transcription. To examine possible cellular signaling mechanisms coupling α7 to Ccl24 transcription, an AM culture model system was used. In AM cultures of freshly collected BALF, Ccl24 transcription was robustly activated by a mixture of IL-4 and IL-10, and this was suppressed by coapplication of type-1 PAMs through a pathway that requires p38MAPK but is independent of Jak2. These results suggest that the EOS response to HDM inhaled allergen is subject to modulation through activation of the α7 receptor and suggest that the allergic response may be substantially modified in ENDS users.

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House dust mite-induced ATP release plays a role in the innate immunological response and barrier dysfunction of airway epithelium

Pneumologie ◽

10.1055/s-0032-1329799 ◽

2012 ◽

Vol 66 (11) ◽

Author(s):

S Post ◽

M Nawijn ◽

A van Oosterhout ◽

I Heijink

Keyword(s):

House Dust ◽

House Dust Mite ◽

Airway Epithelium ◽

Atp Release ◽

Immunological Response ◽

Barrier Dysfunction ◽

Dust Mite

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Safety profile and immunological response of dual sublingual immunotherapy with house dust mite tablet and Japanese cedar pollen tablet

Allergology International ◽

10.1016/j.alit.2019.07.007 ◽

2020 ◽

Vol 69 (1) ◽

pp. 104-110 ◽

Cited By ~ 2

Author(s):

Minoru Gotoh ◽

Kimihiro Okubo ◽

Atsushi Yuta ◽

Yukiko Ogawa ◽

Hitoshi Nagakura ◽

...

Keyword(s):

House Dust ◽

House Dust Mite ◽

Safety Profile ◽

Sublingual Immunotherapy ◽

Immunological Response ◽

Japanese Cedar ◽

Dust Mite ◽

Japanese Cedar Pollen ◽

Cedar Pollen

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Age-dependent pulmonary reactivity to house dust mite allergen: a model of adult-onset asthma?

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00468.2018 ◽

2019 ◽

Vol 316 (5) ◽

pp. L757-L763 ◽

Cited By ~ 1

Author(s):

Savannah Mack ◽

Jinho Shin ◽

Yoomin Ahn ◽

Alejandro R. Castaneda ◽

Janice Peake ◽

...

Keyword(s):

House Dust ◽

House Dust Mite ◽

Age At Onset ◽

Age Groups ◽

Lavage Fluid ◽

Saline Control ◽

Adult Onset ◽

Th2 Response ◽

Dust Mite ◽

Age Dependent

Asthma is a heterogeneous disease differentiated by factors like allergen sensitivity, inflammation, sex, and age at onset. The mouse model is widely used to study the early-life development of allergic asthma. However, age-dependent allergen responses later in life remain relatively understudied and lack a widely accepted model. To differentiate age-dependent responses to the ubiquitous house dust mite (HDM), 3- and 9-mo-old female C57BL/6 mice were randomized into two groups each and exposed to HDM or phosphate-buffered saline (control) via intranasal instillation for sensitization and challenge phases. At 24 h after challenge, all mice underwent pulmonary function testing and methacholine challenge. Bronchoalveolar lavage fluid (BALF) was collected for assessment of cell differentials, and right lung lobes were fixed, sectioned, and stained for histopathology and immunohistochemistry. Both age groups demonstrated strong inflammatory/allergic responses to HDM exposure. However, only 9-mo-old HDM-exposed mice demonstrated significant airway hyperresponsiveness compared with age-matched controls. These HDM-exposed mice also had 1) statistically significant increases in tissue bronchiolitis, perivasculitis, and BALF neutrophilia relative to their younger counterparts and 2) significantly increased extent of immunostaining compared with all other groups. This study presents a potential model for adult-onset asthma, focusing specifically on the atopic, perimenopausal female phenotype. Our findings suggest that lung function declines with age and that the inflammatory profile of this adult subgroup is a mixed, rather than a simple, atopic, Th2 response. This model may enhance our understanding of how age influences the development of asthmic-like symptoms in older subgroups.

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Allergic Responses Induced by a Fungal BiopesticideMetarhizium anisopliaeand House Dust Mite Are Compared in a Mouse Model

Journal of Toxicology ◽

10.1155/2011/360805 ◽

2011 ◽

Vol 2011 ◽

pp. 1-13 ◽

Cited By ~ 4

Author(s):

Marsha D. W. Ward ◽

Yong Joo Chung ◽

Lisa B. Copeland ◽

Donald L. Doerfler

Keyword(s):

House Dust ◽

House Dust Mite ◽

Bronchoalveolar Lavage Fluid ◽

Lavage Fluid ◽

Specific Ige ◽

Response Level ◽

Similar Dose ◽

Dust Mite ◽

Ige Response ◽

Serum Total Ige

Biopesticides can be effective in controlling their target pest. However, research regarding allergenicity and asthma development is limited. We compared the ability of fungal biopesticideMetarhizium anisopliae(MACA) and house dust mite (HDM) extracts to induce allergic responses in BALB/c mice. The extracts were administered by intratracheal aspiration at doubling doses (2.5–80 g protein) 4X over a four-week period. Three days after the last exposure, serum and bronchoalveolar lavage fluid (BALF) were collected. The extracts' relative allergenicity was evaluated based on response robustness (lowest significant dose response compared to control (0 g)). MACA induced a more robust serum total IgE response than HDM. However, in the antigen-specific IgE assay, a similar dose of both MACA and HDM was required to achieve the same response level. Our data suggest a threshold dose of MACA for allergy induction and thatM. anisopliaemay be similar to HDM in allergy induction potential.

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