A novel mouse model of experimental asthma.
BACKGROUND
Animal models that mimic the pulmonary features observed in human asthma are important tools to study the mechanism(s) of allergen-induced asthma. Cockroach and dust mite allergens are two common allergens found in the 'inner city' environment. In this study, we examined the interaction between recombinant cockroach (r Bla g 2) and dust mite (r Der f 1) allergens in inbred mouse strain (A/J). The tested hypothesis was that there are enhanced effects of exposure to r Bla g 2 and r Der f 1 allergens in the airway inflammatory response in A/J mice.


METHODS
Five groups of mice (male, 6-8 weeks) were examined: vehicle (saline) controls; adjuvant (alum) controls; r Bla g 2 immunized (0.01-10 microg/mouse), r Der f 1 immunized (0.01-10 microg/mouse), and combined immunization with r Der f 1 (0.05 microg/mouse) and r Bla g 2 (0.0 5 microg/mouse). Mice were immunized at days 0 and 7, challenged by oro-tracheal inhalation with r Der f 1 and/or r Bla g 2 allergen at day 14, and were studied and sacrificed on day 17. Airway hyperreactivity was measured by peak airway pressure and airway pressure time index (APTI). Differential cell analysis and total proteins in bronchoalveolar lavage returns were used to assess airway inflammation and epithelial injury.


RESULTS
Dose-related statistically significant increases in peak pressure, APTI, total cells, eosinophils, epithelial cells, but not total proteins, were induced by r Bla g 2 challenge in r Bla g 2-immunized mice. Similar allergen-induced dose-related increases in airway total cells, eosinophils, epithelial cells and total proteins were observed in r Der f 1 immunized mice. Compared to either allergen alone, enhanced airway inflammation and epithelial damage, but not airway reactivity, were detected in the combined group.


CONCLUSIONS
This novel mouse model will allow investigation of the immunopathogenesis of human asthma and should provide insight into the common form of 'inner city asthma'.
Sarpong
Sampson B
SB
Department of Pediatrics and Child Health, National Human Genome Center, Howard University, Washington DC 20060, USA. ssarpong@howard.edu
Zhang
Liu-Yi
LY
Kleeberger
Steven R
SR
D000403:Airway Resistance / Q000276:immunology; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology*; D060829:Arthropod Proteins; D016282:Aspartic Acid Endopeptidases / Q000276:immunology*; D001249:Asthma / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002452:Cell Count; D003058:Cockroaches / Q000276:immunology; D003546:Cysteine Endopeptidases; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D006651:Histocytochemistry; D006969:Hypersensitivity, Immediate / Q000276:immunology; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008925:Mites / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D014505:Urban Population
D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D011994:Recombinant Proteins; D003546:Cysteine Endopeptidases; C451159:Dermatophagoides farinae antigen f 1; D016282:Aspartic Acid Endopeptidases; C094699:allergen Bla g 2