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

Abstract

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.

Role of LTB4in the pathogenesis of elastase-induced murine pulmonary emphysema

“…Several postmortem factors such as activation of coagulation, rigor mortem, and techniques to inflate whole lungs may influence and skew experimental endpoints in postmortem anatomic assessment. On the other hand, premortem assessment with Flexivent has been applied with increasing frequency in recent years to provide more in-depth understanding of pulmonary pathology in murine models (9,10,23,24,37). However, to date, only a few studies have utilized both premortem and postmortem assessments to characterize pulmonary emphysema in murine models (28).…”

Zinc oxide nanoparticles induce eosinophilic airway inflammation in mice

“…The solution (50 L) was pipetted to the oropharynx when the mouse's nose was closed. By forcing the mouse to breathe through the mouth, the solution was aspirated to the lower airways [23]. For the ZnO NPs + OVA group, Balb/c mice were treated with 50 L of ZnO NPs 1 h before they were treated with 10 g/50 L OVA.…”

Lung exposure to nanoparticles modulates an asthmatic response in a mouse model

“…On day 14, 40 mL NP suspensions (,0.8 mg?kg -1 TiO 2 and Au) or 2.5 mM trisodium citrate (vehicle) were given via oropharyngeal aspiration under light isoflorane anaesthesia. On day 15, the mice were challenged oropharyngeally with 0.01% TDI as described previously [33]. On day 16, methacholine provocation was performed with the collection of bronchoalveolar lavage (BAL), blood and lung tissue for histology.…”

“…of pentobarbital, blood was sampled from the retro-orbital plexus and a BAL was performed, as described previously [33]. Total and differential cell counts were performed and the BAL supernatant was frozen (-80uC) until further use.…”