Related Experiment Videos
Increased leukotriene E4 excretion during antigen-induced bronchoconstriction in allergic sheep
P Tagari1, W M Abraham, J McGolrick
1Department of Pharmacology, Merck Frosst Centre for Therapeutic Research, Point-Claire, Quebec, Canada.
Journal of Applied Physiology (Bethesda, Md. : 1985)
|April 1, 1990
Summary
Researchers identified leukotriene (LT) metabolites in sheep urine as noninvasive markers for allergic responses. Increased urinary LTE4 levels correlated with allergic bronchoconstriction severity, supporting LT
Area of Science:
- Allergy and Immunology
- Pharmacology and Toxicology
- Respiratory Medicine
Background:
- Leukotrienes (LTs) play a role in allergic responses.
- Identifying noninvasive markers for 5-lipoxygenase involvement is crucial for understanding allergic mechanisms.
- Sheep serve as a relevant animal model for studying prolonged allergic bronchoconstriction.
Purpose of the Study:
- To define noninvasive urinary markers of 5-lipoxygenase activity in allergic responses.
- To investigate leukotriene metabolism in sheep following antigen challenge.
- To correlate leukotriene excretion with the severity of allergic bronchoconstriction.
Main Methods:
- Intravenous administration of radiolabeled leukotriene C4 (LTC4) in sheep.
- Analysis of circulatory and urinary metabolites using reverse-phase high-pressure liquid chromatography (RP-HPLC).
- Quantification of immunoreactive leukotriene E4 (LTE4) in urine via RP-HPLC radioimmunoassay.
- Assessment of pulmonary function and bronchoconstriction severity.
Main Results:
- Rapid clearance of LTC4 from circulation with formation of LTD4 and LTE4.
- Detection of immunoreactive LTE4 in urine of allergic sheep.
- Significantly increased urinary LTE4 excretion during acute antigen-induced bronchoconstriction.
- Strong correlation between total postantigen LTE4 excretion and bronchoconstriction severity.
Conclusions:
- Urinary LTE4 is a valid noninvasive marker for allergen-induced leukotriene generation in vivo.
- These findings demonstrate in vivo allergen-induced peptide LT generation in a physiologically characterized animal model.
- Leukotrienes play a significant role in this model of allergic asthma and bronchoconstriction.