Increased leukotriene E4 excretion during antigen-induced bronchoconstriction in allergic sheep

P. Tagari, W. M. Abraham, J. McGolrick, S. Charleson, M. Soler, A. Ahmed, A. Cortez, A. W. Ford-Hutchinson

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16 Scopus citations

Abstract

The metabolism of leukotrienes (LT) in the sheep was investigated to define markers of 5-lipoxygenase involvement in allergic responses, obtainable by noninvasive techniques. Intravenous administration of 14,15-[3H]LTC4 (0.5 μCi/kg) revealed a rapid clearance from the circulation (half time = 90 s). Circulatory metabolism was apparent, with early formation (within 1 min) of LTD4 and LTE4 shown by reverse-phase high-pressure liquid chromatography (RP-HPLC). Urinary 3H excretion comprised 10% of the original dose. [3H]LTE4 (characterized by coelution with authentic standards during RP-HPLC analysis) was observed in early urine samples. By use of a sensitive and specific RP-HPLC radioimmunoassay analysis, immunoreactive material coeluting with LTE4 was detected in urine from allergic sheep. Excretion of this material was significantly increased during antigen-induced acute bronchoconstriction in eight conscious allergic sheep [preantigen, 65.70 ± 24.27 (SE) pg; 0-1 h postantigen, 208.00 ± 71.10 pg, P < 0.05], but not during late responses. However, total postantigen LTE4 excretion (37.8-956.1 pg/8 h) was highly correlated (r = 0.976, P < 0.001) with the severity of bronchoconstriction (445.3-2,409.1% specific pulmonary resistance per hour) assessed by measurement of the area under the curve of pulmonary function plotted against time. These findings represent an important demonstration of in vivo allergen-induced peptide LT generation in a physiologically characterized animal model of prolonged allergic bronchoconstriction and further substantiate an important role for LT in this model of allergic asthma.

Original languageEnglish (US)
Pages (from-to)1321-1327
Number of pages7
JournalJournal of applied physiology
Volume68
Issue number4
DOIs
StatePublished - 1990

Keywords

  • allergic bronchoconstriction
  • asthma
  • metabolism

ASJC Scopus subject areas

  • Endocrinology
  • Physiology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

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    Tagari, P., Abraham, W. M., McGolrick, J., Charleson, S., Soler, M., Ahmed, A., Cortez, A., & Ford-Hutchinson, A. W. (1990). Increased leukotriene E4 excretion during antigen-induced bronchoconstriction in allergic sheep. Journal of applied physiology, 68(4), 1321-1327. https://doi.org/10.1152/jappl.1990.68.4.1321