Resolution of allergic airways inflammation but persistence of airway smooth muscle proliferation after repeated allergen exposures.
BACKGROUND
Chronic inflammation in asthmatic airways can lead to characteristic airway smooth muscle (ASM) thickening and pathological changes within the airway wall.


OBJECTIVE
We investigated the long-term effects of repeated allergen exposure.


METHODS
Brown-Norway (BN) rats sensitized to ovalbumin (OVA) were exposed to OVA or saline aerosol every third day on six occasions and studied 24 h, 7 days and 35 days after the final exposure. We measured airway inflammation, ASM cell proliferation (by incorporation of bromodeoxyuridine; BrdU) and bronchial responsiveness to acetylcholine.


RESULTS
At 24 h, in OVA-exposed rats, we detected elevated OVA-specific serum IgE, increased numbers of macrophages, eosinophils, lymphocytes and neutrophils in the bronchoalveolar lavage (BAL) fluid and increased numbers of MBP+ (major basic protein) eosinophils and CD2+ T cells within the bronchial submucosa. This coincided with increased numbers of ASM cells expressing BrdU and with bronchial hyper-responsiveness (BHR). At 7 days, BHR was detected in OVA-exposed rats, coincident with increased numbers of macrophages and lymphocytes in BAL fluid together with increased numbers of CD2+ T cells within the bronchial submucosa. This coincided with increased numbers of ASM cells expressing BrdU. By day 35, the number of ASM cells expressing BrdU remained elevated in the absence of cellular infiltration and BHR.


CONCLUSIONS
Repeated OVA-challenge results in persistent ASM cell proliferation in the absence of bronchial inflammation and BHR, which lasts for at least 1 week following cessation of exposure.
Thoracic Medicine, National Heart and Lung Institute, Imperial College, London, UK.
S-Y
SY
Leung
P
P
Eynott
A
A
Noble
P
P
Nath
K F
KF
Chung
D000485:Allergens / Q000008:administration & dosage*; D000818:Animals; D001249:Asthma / Q000276:immunology*; D001980:Bronchi / Q000276:immunology / Q000473:pathology*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D018801:CD2 Antigens / Q000032:analysis; D002455:Cell Division; D004804:Eosinophils / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D007962:Leukocytes / Q000276:immunology; D008297:Male; D009130:Muscle, Smooth / Q000276:immunology / Q000473:pathology*; D010047:Ovalbumin; D051381:Rats; D011914:Rats, Inbred BN; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
D000485:Allergens; D018801:CD2 Antigens; D007073:Immunoglobulin E; D010047:Ovalbumin