Respiratory sensitization and allergy: Current research approaches and needs

Boverhof, Darrell R.; Billington, Richard; Gollapudi, B. Bhaskar; Hotchkiss, John A.; Krieger, Shannon M.; Poole, Alan; Wiescinski, Connie M.; Woolhiser, Michael R.

doi:10.1016/j.taap.2007.10.008

Cited by 86 publications

(61 citation statements)

References 77 publications

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“…In another study, asthmatic volunteers showed a striking bronchial constriction following exposure to starch granules only [17]. Bronchoconstriction was not assessed herein because Brown Norway rats are not a good model for this parameter [33,34]. …”

Section: Discussionmentioning

confidence: 99%

Ability of Pollen Cytoplasmic Granules to Induce Biased Allergic Responses in a Rat Model

Chakra¹,

Rogerieux

Poncet³

et al. 2010

Int Arch Allergy Immunol

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Background: Grass pollen is one of the most important aeroallergens in Europe. It highly contributes to respiratory allergic diseases, mainly allergic rhinitis. In contact to water or airborne pollutants, pollen grains can release pollen cytoplasmic granules (PCGs) containing allergens. Because of their size (<5 µm), PCGs may penetrate deeper into the lungs to induce higher allergic responses, such as asthma. They have been associated with thunderstorm-related asthma. The aim of this study was to evaluate, with Brown Norway rats, the allergenic potential of isolated PCGs and to compare it with the allergenicity of whole timothy grass pollen. Methods: Rats were sensitized (day 0) and challenged (day 21), in controlled comparative conditions, with pollen grains (0.5 mg) or PCGs (4.5 × 10⁷ and 0.5 mg). At day 25, blood samples, bronchoalveolar lavage fluid (BALF) and bronchial lymph node were collected. IgE and IgG1 levels in sera were assessed by ELISA. Alveolar cells, protein and cytokine concentrations were quantified in BALF. T cell proliferation, in response to pollen or granules, was performed by lymph node assay. Results: The results showed that proliferative responses of lymph node cells were similar in PCG- and pollen-sensitized rats. IgE and IgG1 levels were higher in pollen- than in PCG-sensitized rats. However, eosinophils, lymphocytes and pro-allergy cytokines in BALF were higher in PCG- than in pollen-sensitized rats. Conclusions: Thus, PCGs, able to deeply penetrate in the respiratory tract, induced local and strong allergic and inflammatory responses more linked with asthma- than rhinitis-related allergic symptoms.

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Section: Discussionmentioning

confidence: 99%

Ability of Pollen Cytoplasmic Granules to Induce Biased Allergic Responses in a Rat Model

Chakra¹,

Rogerieux

Poncet³

et al. 2010

Int Arch Allergy Immunol

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“…Research indicates that respiratory sensitizers may be identified through contact sensitization assays such as the LLNA, as all low-molecular-weight respiratory sensitizers tested so far were also positive in this assay (Arts et al, 2008;Boverhof et al, 2008). The unique defining characteristic of chemical respiratory allergens, which in most instances distinguishes them from contact allergens, is the ability to provoke the preferential development of T H 2-type immune responses (Kimber and Dearman, 2005).…”

Section: In Vitro Assessment Of Respiratory Sensitizersmentioning

confidence: 99%

Present and future ofin vitroimmunotoxicology in drug development

Galbiati

Mitjans

Corsini

2010

Journal of Immunotoxicology

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“…Although the usefulness of animal models for studying human asthma has been heavily debated, the number of murine studies published, increases every year (Wenzel and Holgate, 2006). The use of mice is justified by the fact that the specific molecular pathways are similar to those of humans, and also because of their well-characterized immune system, their fully sequenced genome, the existence of various genetically modified models and the availability of mousespecific reagents (Boverhof et al, 2008;Shapiro, 2006). Because mice do not spontaneously exhibit symptoms consistent with asthma, they must be sensitized and challenged with an allergen or a chemical agent.…”

Section: Introductionmentioning

confidence: 99%

Oropharyngeal aspiration: An alternative route for challenging in a mouse model of chemical-induced asthma

et al. 2009

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a b s t r a c tBackground: To assess the importance of the route of challenge in an existing mouse model of chemicalinduced asthma, we replaced intranasal instillation by oropharyngeal aspiration. To our knowledge, oropharyngeal aspiration as a challenge route has not yet been investigated in a mouse model of chemicalinduced asthma. Methods: On days 1 and 8, mice were dermally sensitized with toluene diisocyanate (TDI) (0.3%) [or vehicle (acetone/olive oil)] and on day 15 they received a single challenge, via oropharyngeal aspiration, with TDI (0.01%) or vehicle. One day after challenge, airway reactivity to methacholine was measured by a forced oscillation technique (FlexiVent) and total and differential cell counts, as well as levels of KC, IL-5, IL-17 and TNF-␣, were assessed in the bronchoalveolar lavage (BAL) fluid. Lymphocytes from the auricular and mediastinal lymph nodes were cultured to determine the concanavaline A-induced secretion of IL-2, IL-4, IL-10, IL-13, IL-17 and IFN-␥. Total serum IgE was measured. Results: In TDI-sensitized mice, a significant increase in airway reactivity was found after a single oropharyngeal challenge with TDI. BAL neutrophils and eosinophils were increased 7-and 5-fold, respectively. An upregulation of Th1 (IFN-␥), Th2 (IL-4, IL-10, IL-13) and Th17 (IL-17) cytokines was found in the auricular lymph nodes, in the mediastinal lymph nodes only IL-4 was upregulated. The total serum IgE level in TDI-sensitized mice was significantly increased when compared to control mice. Conclusion: We conclude that challenging mice via oropharyngeal aspiration mimics the characteristics of human asthma well, without the possible drawbacks of other techniques.

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Respiratory sensitization and allergy: Current research approaches and needs

Cited by 86 publications

References 77 publications

Ability of Pollen Cytoplasmic Granules to Induce Biased Allergic Responses in a Rat Model

Ability of Pollen Cytoplasmic Granules to Induce Biased Allergic Responses in a Rat Model

Present and future ofin vitroimmunotoxicology in drug development

Oropharyngeal aspiration: An alternative route for challenging in a mouse model of chemical-induced asthma

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