Allergen-induced increase in airway responsiveness, airway eosinophilia, and bone-marrow eosinophil progenitors in mice

Increases in bone-marrow (BM) inflammatory cell progenitors are associated with allergen-induced airway hyperresponsiveness and inflammation in asthma tics and dogs. Here, for the first time, we compare the time course of airw ay hyperresponsiveness, inflammation, and marrow progenitor responses in a mouse model of airway allergen challenge. Sensitized BALB/c mice were studi ed at 2, 12, 24, 48, and 72 h after intranasal ovalbumin or saline challeng es. Outcome measurements included airway responsiveness, airway inflammatio n as assessed via bronchoalveolar lavage (BAL) and lung tissue sections, an d BM eosinophil colony-forming units (Eo-CFU) as enumerated using a semisol id culture assay with optimal concentrations of interleukin-5. We observed significant increases in BAL fluid eosinophils, neutrophils, lymphocytes, a nd macrophages by 2 h after the second of two intranasal allergen challenge s (P < 0.05). Significant increases in airway responsiveness or BM Eo-CFU w ere observed at 24 h and persisted until 48 h after the second challenge (P < 0.05). Airway inflammation, including eosinophils, persisted until at le ast 72 h (P < 0.05). We observed that allergen-induced airway eosinophilia is accompanied by increases in BM eosinophil progenitors, indicating that i n this model, increased eosinophil production involves an expansion of the relevant stem-cell population. These findings support the use of this model to explore the mechanisms of increased eosinopoiesis observed in human ast hma.