Asthma progression to airway remodeling and bone marrow eosinophil responses in genetically distinct strains of mice.
Hogan-MB; Piktel-D; Hubbs-AF; McPherson-LE; Landreth-KS
Ann Allergy, Asthma, & Immun 2008 Dec; 101(6):619-625
Background: patient factors that cause long-term airway remodeling are largely unidentified. This Suggests that genetic differences may determine which asthmatic patients develop airway remodeling. A murine model with repeated allergen exposure leading to peribronchial fibrosis in complement factor 5 (C5)-deficient A/J mice has been used to study asthma progression. No Studies have addressed the systemic effects of allergen sensitization or chronic allergen exposure on bone marrow eosinophilopoiesis in this mouse strain. Objective: to investigate bone marrow eosinophil responses during acute sensitization and chronic allergen exposure using genetically distinct mouse strains differing in persistent airway reactivity and remodeling. Methods: the C5-sufficient BALB/c and C5-deficient A/J mice were repetitively exposed to intranasal ovalbumin for 12 weeks. Subsequently, the mice were evaluated for airway eosinophilia, mucus-containing goblet cells, and peribronchial fibrosis. Both strains of mice were also acutely sensitized to ovalbumin. Bone marrow eosinophil progenitor cells and mature eosinophils were enumerated. Results: BALB/c and A/J mice have similar bone marrow responses after acute allergen exposure, with elevations in bone marrow eosinophil progenitor cell and eosinophil numbers. After chronic allergen exposure, only C5-deficient A/J mice that developed peribronchial fibrosis exhibited bone marrow eosinophilia. BALB/c mice lacked peribronchial fibrosis and extinguished accelerated eosinophil production after long-term allergen challenge. Conclusions: chronic airway remodeling after repeated allergen exposure in genetically different mice correlated with differences in long-term bone marrow eosinophilopoiesis. Preventing asthma from progressing to chronic airway remodeling with fibrosis may involve identifying genetically determined influences on bone marrow responses to chronic allergen exposure.
Air-quality; Airway-obstruction; Allergic-disorders; Allergies; Antibody-response; Antigens; Breathing; Breathing-zone; Laboratory-animals; Laboratory-testing; Genetic-factors; Lung; Lung-irritants; Pulmonary-system-disorders; Bronchial-asthma; Bone-marrow; Immune-reaction; Immune-system-disorders
Mary Beth Hogan, University of Nevada, School of Medicine, Department of Pediatrics, 343 Elm St,Ste 201, Reno, NV 89503
Annals of Allergy, Asthma, and Immunology