Aerosolized LTB4 produces delayed onset increases in pulmonary gas trapping.
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.
Silbaugh
S A
SA
Lilly Research Laboratories, Ell Lilly and Company, Indianapolis, IN 46285, USA.
Stengel
P W
PW
Cockerham
S L
SL
Froelich
L L
LL
Bendele
A M
AM
Rippy
M K
MK
Baker
S R
SR
Sofia
M J
MJ
Jackson
W T
WT
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
D000336:Aerosols; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001578:Benzopyrans; D016861:Cyclooxygenase Inhibitors; D018102:Receptors, Leukotriene B4; C059950:SC 41930; D007975:Leukotriene B4