Involvement of Mast Cells in Adenosine-Mediated Bronchoconstriction and Inflammation in an Allergic Mouse Model

Abstract

In allergen-induced asthma, activation of lung mast cells leads to bronchial constriction, increased mucus secretion, and an increase in the localization of inflammatory cells to the airways. The purpose of this study was to explore the role of mast cells in adenosine-mediated airway reactivity and inflammation using the mast cell degranulating agent, compound 48/80 (C48/80). Mice were sensitized and challenged with ragweed (or 0.9% saline) followed by C48/80 administration twice a day in increasing doses for 5 days. Dose-responsiveness to the nonspecific adenosine receptor agonist 5Ј-N-ethylcarboxamidoadenosine (NECA) was established, and lung lavage was performed 24 h later for cell differential analysis to evaluate inflammation. At a dose of 375 g/ml (aerosolized NECA), C48/80 pretreatment resulted in a significant attenuation in airway reactivity when compared with sensitized control mice (330.07 versus 581.57%, respectively). Lung lavage from the C48/80 treated mice showed a decrease in eosinophils (17.7 versus 60.9%, respectively) and an increase in macrophages when compared with the sensitized control group (76.4 versus 30.8%, respectively). These results support the conclusion that mast cell degranulation plays an important role in adenosine receptor-mediated airway hyperresponsiveness and inflammation.

Involvement of A1adenosine receptors in altered vascular responses and inflammation in an allergic mouse model of asthma

“…Whole body plethysmography has been used previously to determine the extent of airway hyperresponsiveness and as a measure of airway obstruction (12,17,18,45). We used this method to determine the differences between A 1 WT and A 1 KO responses to MCh and NECA.…”

Purinergic Signaling in the Airways

“…In other mouse allergy models, A 2B receptors were identified as the main receptor subtype involved in increases in ion transport (Kornerup et al, 2005;Mustafa et al, 2007). Mast cells were shown to be involved in adenosine-mediated bronchoconstriction and inflammation in an allergic mouse model (Oldenburg and Mustafa, 2005). Mast cells were claimed to be activated after adenosine challenge in allergic, but not nonallergic, patients with asthma (Bochenek et al, 2008).…”

Effect of a Specific and Selective A2BAdenosine Receptor Antagonist on Adenosine Agonist AMP and Allergen-Induced Airway Responsiveness and Cellular Influx in a Mouse Model of Asthma

“…On day 14, mice were challenged with NECA, AMP, or allergen, and the airway reactivity was measured using barometric plethysmography Mustafa, 2002, 2006;Oldenburg and Mustafa, 2005). It has been previously shown that changes (increases or decreases) in Penh correlate with changes (increases or decreases) in airway resistance in this model (Justice et al, 2001).…”