title: Aerosolized LTB4 produces delayed onset increases in pulmonary gas trapping.
abstract: Airway obstruction, as measured by increases in postmortem pulmonary gas trapping, and lung inflammatory changes were examined in guinea pigs exposed for up to 4 h to aerosols of leukotriene B4 (LTB4) or its non-chemotactic isomer, 6-trans-12-epi-LTB4. Airway obstruction and cytological responses in isomer-exposed animals were similar to those of unexposed control animals. LTB4-exposed animals had minimal inflammatory changes at 0.5 h but became dyspneic by 2 h and had increased airway obstruction, bronchoalveolar lavage neutrophils and eosinophils, and pulmonary tissue granulocyte scores. The LTB4-induced effects at 4 h were similar to those 2 h, except for further increase in BAL neutrophils and eosinophils. LTB4-induced airway obstructive and inflammatory changes were prevented by pretreatment with the LTB4 receptor antagonist SC-41930, but were unaffected by indomethacin. Thus, prolonged LTB4 inhalation can produce delayed onset airway obstruction that is stereospecific, cyclooxygenase-independent, and temporally associated with the influx of granulocytes into lung airways.
authors.affiliation: Lilly Research Laboratories, Ell Lilly and Company, Indianapolis, IN 46285, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Silbaugh
authors.forename: P W
authors.initials: PW
authors.lastname: Stengel
authors.forename: S L
authors.initials: SL
authors.lastname: Cockerham
authors.forename: L L
authors.initials: LL
authors.lastname: Froelich
authors.forename: A M
authors.initials: AM
authors.lastname: Bendele
authors.forename: M K
authors.initials: MK
authors.lastname: Rippy
authors.forename: S R
authors.initials: SR
authors.lastname: Baker
authors.forename: M J
authors.initials: MJ
authors.lastname: Sofia
authors.forename: W T
authors.initials: WT
authors.lastname: Jackson
mesh_terms: D000336:Aerosols; D000402:Airway Obstruction / Q000139:chemically induced* / Q000473:pathology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D018893:Bronchoalveolar Lavage; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D006098:Granulocytes / Q000473:pathology; D006168:Guinea Pigs; D007249:Inflammation / Q000473:pathology; D007975:Leukotriene B4 / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008176:Lung Volume Measurements; D008297:Male; D008853:Microscopy; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors; D013237:Stereoisomerism
chemical_list: D000336:Aerosols; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001578:Benzopyrans; D016861:Cyclooxygenase Inhibitors; D018102:Receptors, Leukotriene B4; C059950:SC 41930; D007975:Leukotriene B4