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CHARACTERIZATION OF IMMEDIATE AND LATE PHASE AIRWAY RESPONSES TO HOUSE DUST MITE CHALLENGE IN BROWN NORWAY RATS AND CORRELATIONS AMONG PHYSIOLOGICAL MEDIATORS
Citation:
Singh, P., D. W. Winsett, M. J. Daniels, J. Richards, K Crissman, D L. Doerfler, AND M I. Gilmour. CHARACTERIZATION OF IMMEDIATE AND LATE PHASE AIRWAY RESPONSES TO HOUSE DUST MITE CHALLENGE IN BROWN NORWAY RATS AND CORRELATIONS AMONG PHYSIOLOGICAL MEDIATORS. Presented at American Thoracic Society, Atlanta, GA, May 17-22, 2002.
Description:
CHARACTERIZATION OF IMMEDIATE AND LATE PHASE AIRWAY RESPONSES TO HOUSE DUST MITE CHALLENGE IN BROWN NORWAY RATS AND CORRELATIONS AMONG PATHOPHYSIOLOGICAL MEDIATORS (P.
SinghI, D.W. Winsett2, M.J. Daniels2, J. Richards2, K. Crissman2, D.L. Doerfler2 and M.I. Gilmour2, 1NCSU, Raleigh, N.C. and 2NHEERL/ORD/ USEPA, RTP, N.C.) The human asthmatic response frequently demonstrates biphasic bronchoconstriction consisting of an immediate and a late phase. In allergic asthma, the immediate airway response (JAR) to allergen occurs within 10-30 min after challenge and usually resolves within 1-2 hr. A more sustained, late airway response (LAR) may follow, usually beginning between 3-5 hr and often persisting more than 24 hr after allergen challenge. In the present study, we wanted to determine how closely our rat model of allergic airway disease mimics human allergic asthma. To do this, we investigated the kinetics of airway responses to house dust mite (HDM) challenge over 8 hr in both locally and systemically sensitized Brown Norway (BN) rats. We also evaluated lung inflammation and injury 2 days after allergen challenge to establish correlations among pathophysiological responses to HDM. The IAR peaked at 1 hr post HDM challenge in systemically sensitized rats, while in locally sensitized rats, the peak occurred at 3 hr post challenge. Systemic sensitization produced a more pronounced IAR than local sensitization; however, airway responses to HDM challenge were still significantly elevated 24 hr after allergen challenge, regardless of route of sensitization. In addition, we found significant correlations among measures of inflammation and lung injury in the bronchoalveolar lavage fluid including TNFa, total protein, MIP-2, inflammatory cells and antioxidant levels. In conclusion, the present study provides evidence of a prolonged airway response to HDM challenge in BN rats that is not biphasic but persists into the late phase response, possibly in association with multiple inflammatory processes in the lung.