Asthma progression to airway remodeling and bone marrow eosinophil responses in genetically distinct strains of mice.
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.
Hogan
Mary Beth
MB
Department of Pediatrics, University of Nevada School of Medicine, Reno, Nevada 89503, USA. mbhogan@medicine.nevada.edu
Piktel
Debra
D
Hubbs
Ann F
AF
McPherson
Leslie E
LE
Landreth
Kenneth S
KS
D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000473:pathology*; D001853:Bone Marrow / Q000276:immunology*; D001980:Bronchi / Q000276:immunology / Q000473:pathology*; D002908:Chronic Disease; D015936:Complement C5a / Q000235:genetics*; D004195:Disease Models, Animal; D018450:Disease Progression; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D005355:Fibrosis; D007958:Leukocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology
D000485:Allergens; D015936:Complement C5a; D010047:Ovalbumin