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 asthmatics and dogs. Here, for the first time, we compare the time course of airway hyperresponsiveness, inflammation, and marrow progenitor responses in a mouse model of airway allergen challenge. Sensitized BALB/c mice were studied at 2, 12, 24, 48, and 72 h after intranasal ovalbumin or saline challenges. Outcome measurements included airway responsiveness, airway inflammation as assessed via bronchoalveolar lavage (BAL) and lung tissue sections, and BM eosinophil colony-forming units (Eo-CFU) as enumerated using a semisolid culture assay with optimal concentrations of interleukin-5. We observed significant increases in BAL fluid eosinophils, neutrophils, lymphocytes, and macrophages by 2 h after the second of two intranasal allergen challenges (P < 0.05). Significant increases in airway responsiveness or BM Eo-CFU were observed at 24 h and persisted until 48 h after the second challenge (P < 0.05). Airway inflammation, including eosinophils, persisted until at least 72 h (P < 0.05). We observed that allergen-induced airway eosinophilia is accompanied by increases in BM eosinophil progenitors, indicating that in 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 asthma.
Inman
M D
MD
Asthma Research Group, McMaster University, Hamilton, Ontario, Canada. inmanma@fhs.mcmaster.ca
Ellis
R
R
Wattie
J
J
Denburg
J A
JA
O'Byrne
P M
PM
D000485:Allergens / Q000008:administration & dosage*; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000473:pathology; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000209:etiology* / Q000473:pathology; D003114:Colony-Forming Units Assay; D004195:Disease Models, Animal; D004285:Dogs; D004802:Eosinophilia / Q000209:etiology* / Q000473:pathology; D004804:Eosinophils / Q000187:drug effects / Q000473:pathology; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D015848:Interleukin-5 / Q000494:pharmacology; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology
D000485:Allergens; D015848:Interleukin-5; D016210:Methacholine Chloride; D010047:Ovalbumin