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

Research output: Contribution to journalArticle

15 Citations (Scopus)

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
Pages (from-to)1321-1327
Number of pages7
JournalJournal of Applied Physiology
Volume68
Issue number4
StatePublished - Jan 1 1990
Externally publishedYes

Fingerprint

Leukotriene E4
Bronchoconstriction
Leukotrienes
Sheep
Reverse-Phase Chromatography
Antigens
High Pressure Liquid Chromatography
Urine
Leukotriene D4
Arachidonate 5-Lipoxygenase
Lung
Intravenous Administration
Allergens
Area Under Curve
Radioimmunoassay
Asthma
Animal Models
Peptides

Keywords

  • allergic bronchoconstriction
  • asthma
  • metabolism

ASJC Scopus subject areas

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

Cite this

Tagari, P., Abraham, W. M., McGolrick, J., Charleson, S., Soler, M., Ahmed, 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.

Increased leukotriene E4 excretion during antigen-induced bronchoconstriction in allergic sheep. / Tagari, P.; Abraham, W. M.; McGolrick, J.; Charleson, S.; Soler, M.; Ahmed, A.; Cortez, A.; Ford-Hutchinson, A. W.

In: Journal of Applied Physiology, Vol. 68, No. 4, 01.01.1990, p. 1321-1327.

Research output: Contribution to journalArticle

Tagari, P, Abraham, WM, McGolrick, J, Charleson, S, Soler, M, Ahmed, A, Cortez, A & Ford-Hutchinson, AW 1990, 'Increased leukotriene E4 excretion during antigen-induced bronchoconstriction in allergic sheep', Journal of Applied Physiology, vol. 68, no. 4, pp. 1321-1327.
Tagari P, Abraham WM, McGolrick J, Charleson S, Soler M, Ahmed A et al. Increased leukotriene E4 excretion during antigen-induced bronchoconstriction in allergic sheep. Journal of Applied Physiology. 1990 Jan 1;68(4):1321-1327.
Tagari, P. ; Abraham, W. M. ; McGolrick, J. ; Charleson, S. ; Soler, M. ; Ahmed, A. ; Cortez, A. ; Ford-Hutchinson, A. W. / Increased leukotriene E4 excretion during antigen-induced bronchoconstriction in allergic sheep. In: Journal of Applied Physiology. 1990 ; Vol. 68, No. 4. pp. 1321-1327.
@article{3898ac12f5bd4c6f9413dd503d8b6db1,
title = "Increased leukotriene E4 excretion during antigen-induced bronchoconstriction in allergic sheep",
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.",
keywords = "allergic bronchoconstriction, asthma, metabolism",
author = "P. Tagari and Abraham, {W. M.} and J. McGolrick and S. Charleson and M. Soler and A. Ahmed and A. Cortez and Ford-Hutchinson, {A. W.}",
year = "1990",
month = "1",
day = "1",
language = "English",
volume = "68",
pages = "1321--1327",
journal = "Journal of Applied Physiology",
issn = "8750-7587",
publisher = "American Physiological Society",
number = "4",

}

TY - JOUR

T1 - Increased leukotriene E4 excretion during antigen-induced bronchoconstriction in allergic sheep

AU - Tagari, P.

AU - Abraham, W. M.

AU - McGolrick, J.

AU - Charleson, S.

AU - Soler, M.

AU - Ahmed, A.

AU - Cortez, A.

AU - Ford-Hutchinson, A. W.

PY - 1990/1/1

Y1 - 1990/1/1

N2 - 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.

AB - 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.

KW - allergic bronchoconstriction

KW - asthma

KW - metabolism

UR - http://www.scopus.com/inward/record.url?scp=0025193664&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025193664&partnerID=8YFLogxK

M3 - Article

C2 - 2161409

AN - SCOPUS:0025193664

VL - 68

SP - 1321

EP - 1327

JO - Journal of Applied Physiology

JF - Journal of Applied Physiology

SN - 8750-7587

IS - 4

ER -