Validation of a mouse model of chemical-induced asthma using trimellitic anhydride, a respiratory sensitizer, and dinitrochlorobenzene, a dermal sensitizer

Vanoirbeek, Jeroen; Tarkowski, Maciej; Vanhooren, Hadewijch M.; Vooght, Vanessa De; Nemery, Benoît; Hoet, Peter

doi:10.1016/j.jaci.2006.01.027

Cited by 76 publications

(50 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We based our animal model and exposure protocol on previously published data that showed early and late ventilatory changes after 2 dermal skin exposures and one intranasal challenge with TDI [12] which coincided with lung inflammation. Furthermore, these observations were confirmed also for another asthmogen, TMA, but not DNCB [13] and were due to antigen-specific immunological responses [14]. Following similar protocol, first we sought to determine the ability of chemicals to be irritants or specific immune stimulants based on the marker of T cell activation, CD44, described earlier by other authors [24,25].…”

Section: Fig 5 Il-4 and Ifn-γ Gene Expression In Auricular Lymph Nomentioning

confidence: 55%

“…This model still needs further investigations, which would include extension of the list of cytokines for which RealTime PCR would be performed and other chemicals. Together with previously published data [13,14] our model should include also ventilatory measurements that are complementary with immunological parameters in the way to indicate the chemical potentials of respiratory sensitization.…”

Section: Fig 5 Il-4 and Ifn-γ Gene Expression In Auricular Lymph Nomentioning

confidence: 99%

See 1 more Smart Citation

Comparative Studies of Lymph Node Cell Subpopulations and Cytokine Expression in Murine Model for Testing the Potentials of Chemicals to Induce Respiratory Sensitization

Tarkowski

Kur²,

Polakowska³

et al. 2008

International Journal of Occupational Medicine and Environmental Health

Self Cite

View full text Add to dashboard Cite

Objectives: To investigate immunological changes in lymph nodes based on expression of cell-specific receptors and cytokine expression profile and accompanying inflammatory reactions in lungs of mice treated with chemicals of known potentials to induce respiratory sensitization and those in which activity in this regard is unclear. Materials and Methods: On day 1 and 7, Balb/c mice received toluene-2,4-diisocyanate (TDI), trimellitic anhydride (TMA), 1-chloro-2,4-dinitrobenzene (DNCB), glutaraldehyde (GA), formaldehyde (FA), benzalkonium chloride (ChB) or vehicle. On day 14, they received a single intranasal instillation with the same chemical or vehicle. On day 15, auricular lymph nodes (LN) were excised and used for analyzes of T-, B-cells, expression of CD44 and for the estimation of IL-4 and IFN-γ production after in vitro stimulation with concanavalin A (ConA) and also for IL-4 and IFN-γ mRNA expression analyses using Real-Time PCR. Inflammatory changes in lungs were observed by estimation of TNF-α and MIP-2 concentrations and cell numbers and their type in BAL. Results: There were no significant changes in cell subpopulations of T helper cells in LN. The percent of B cells was significantly increased after treatment with DNCB, TDI, and GA. Increased expression of CD44 on T cells was also observed. Both IL-4 and IFN-γ were found increased in TDI-and FA-treated mice, while only IL-4 was increased in TMA-treated mice. Real-Time PCR analyses, however, showed increased IL-4 mRNA expression for TDI-and TMA-, and IFN-γ mRNA expression for DNCB-treated mice. We haven't observed significant changes in inflammatory reactions in the lungs of exposed animals. Conclusions: Studying immunological changes with first determining the activation status of T cells followed by analyzes of expression of mRNA for Th1 and Th2 cytokines in murine model could be a useful method for assessment of the potentials of chemicals to induce respiratory sensitization but is not sufficient. Addition of ventilatory measurements, but not necessarily inflammatory reactions, could complete the model.

show abstract

Section: Fig 5 Il-4 and Ifn-γ Gene Expression In Auricular Lymph Nomentioning

confidence: 55%

Section: Fig 5 Il-4 and Ifn-γ Gene Expression In Auricular Lymph Nomentioning

confidence: 99%

Comparative Studies of Lymph Node Cell Subpopulations and Cytokine Expression in Murine Model for Testing the Potentials of Chemicals to Induce Respiratory Sensitization

Tarkowski

Kur²,

Polakowska³

et al. 2008

International Journal of Occupational Medicine and Environmental Health

Self Cite

View full text Add to dashboard Cite

show abstract

“…In some protocols, the instilled volumes ranged from 50 μl [5,9,12] to 100 μl over several days [6]. Other authors use only 10 μl over several days [14]. We compared the effect of two different volumes of instillation, 15 and 30 μl, and found significant differences between them: The animals that received 15 μl showed approximately 35% less activity in the lungs than those that received 30 μl.…”

Section: Discussionmentioning

confidence: 98%

Assessment of Airway Distribution of Transnasal Solutions in Mice by PET/CT Imaging

et al. 2009

View full text Add to dashboard Cite

Purpose: Transnasal administration is one of the most common routes for allergen challenge in mouse models of airway diseases. Although this technique is widely used, neither the amount of allergen that reaches the lung nor its airway distribution has been well established. We used positron emission tomography (PET) and computed tomography (CT) to examine the anatomical distribution of a solution containing a tracer immediately after transnasal delivery and to determine the possible influence of age and administered volume. Procedures: Forty-six female BALB/c mice were divided into three groups according to instillation volume and age: (A) 15 μl, 8-10 weeks old (N=10), (B) 30 μl, 8-10 weeks old (N= 20), and (C) 30 μl, 32 weeks old (N=16). Anesthetized animals underwent a dynamic scan in a dedicated small-animal PET scanner immediately after transnasal administration of a solution containing 18 FDG. Regions of interest were used to obtain quantitative data. Animals were also imaged with a small-animal CT scanner to obtain complementary anatomical information. Results: Mean±SD (5.69±4.51%) of the solution administered reached the lungs in group A, 41.84±8.03% in group B, and 36.65±16.15% in group C. A comparable percentage was delivered to the left and right lungs in all the groups. Analysis of variance revealed a significant difference between the groups in the proportion of the solution that reached the lungs depending on the injection volume (PG0.001), but not depending on animal age. Conclusions: In this first report on quantitative imaging by PET and CT in small animals, we confirmed the suitability of the transnasal route with an instilled volume of 30 μl delivering fluids into the lower airways, although only about 40% of the dose reaches the lungs.

show abstract

“…Transgenic mouse models have also demonstrated that isocyanates can induce mixed Th1/Th2 responses, and that the immune response is also dependent on the mouse strain (13,15). Similar asthma models involving skin sensitization followed by inhalation challenge have been developed with other chemicals, such as trimellitic anhydride (18).…”

Section: Animal Models Of Chemical and Protein Allergen Skin Exposurementioning

confidence: 99%

Skin Exposure and Asthma: Is There a Connection?

Redlich¹

2010

Proceedings of the American Thoracic Society

101

View full text Add to dashboard Cite

Numerous occupational and environmental exposures that increase asthma risk have been identified. Research and prevention have focused primarily on the respiratory tract. However, recent studies suggest that the skin may also be an important route of exposure and site of sensitization that contributes to asthma development. Factors that impair skin barrier function, such as filaggrin gene mutations or skin trauma, may facilitate allergen entry and promote Th2-like sensitization and subsequent asthma. Animal studies demonstrate that skin exposure to chemical and protein allergens is highly effective at inducing sensitization, with subsequent inhalation challenge eliciting asthmatic responses. A similar role for human skin exposure to certain sensitizing agents, such as isocyanates, is likely. Skin exposure methodologies are being developed to incorporate skin exposure assessment into epidemiology studies investigating asthma risk factors.Keywords: skin exposure; asthma; isocyanates; epidermal barrier function; sensitization Environmental and occupational asthma research and practice have focused primarily on the respiratory tract as the key route of exposure and pathogenesis. However, several lines of research support an important role for skin exposure in initiating and driving Th2-like immune responses and asthma. Human and animal studies of atopic dermatitis have identified skin epithelial barrier dysfunction, which may facilitate allergen entry, as a key factor in the development of atopic asthma and sensitization. This article highlights recent findings from a diverse literature that support the concept that skin may be an important site of exposure for certain occupational and environmental allergens.

show abstract

Validation of a mouse model of chemical-induced asthma using trimellitic anhydride, a respiratory sensitizer, and dinitrochlorobenzene, a dermal sensitizer

Abstract: In the workplace avoiding skin contact with chemical sensitizers might be advised to prevent chemical-induced asthma.

Cited by 76 publications

References 39 publications

Comparative Studies of Lymph Node Cell Subpopulations and Cytokine Expression in Murine Model for Testing the Potentials of Chemicals to Induce Respiratory Sensitization

Comparative Studies of Lymph Node Cell Subpopulations and Cytokine Expression in Murine Model for Testing the Potentials of Chemicals to Induce Respiratory Sensitization

Assessment of Airway Distribution of Transnasal Solutions in Mice by PET/CT Imaging

Skin Exposure and Asthma: Is There a Connection?

Contact Info

Product

Resources

About