AEROSOLIZED LTB(4) PRODUCES DELAYED-ONSET INCREASES IN PULMONARY GAS TRAPPING

Airway obstruction, as measured by increases in postmortem pulmonary g as trapping, and lung inflammatory changes were examined in guinea pig s exposed for up to 4 h to aerosols of leukotriene B-4 (LTB(4)) or its non-chemotactic isomer, 6-trans-12-epi-LTB(4). Airway obstruction and cytological responses in isomer-exposed animals were similar to those of unexposed control animals. LTB(4)-exposed animals had minimal infl ammatory changes at 0.5 h but became dyspneic by 2 h and had increased airway obstruction, bronchoalveolar ravage neutrophils and eosinophil s, and pulmonary tissue granulocyte scores. The LTB(4)-induced effects at 4 h were similar to those at 2 h, except for further increases in BAL neutrophils and eosinophils. LTB(4)-induced airway obstructive and inflammatory changes were prevented by pretreatment with the LTB(4) r eceptor antagonist SC-41930, but were unaffected by indomethacin. Thus , prolonged LTB(4) inhalation can produce delayed onset airway obstruc tion that is stereospecific, cyclooxygenase-independent, and temporall y associated with the influx of granulocytes into lung airways.