Production of early and late pulmonary responses with inhaled leukotriene D4 in allergic sheep

William W Abraham, E. Russi, A. Wanner, J. C. Delehunt, L. D. Yerger, G. A. Chapman

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Some allergic sheep respond to inhalation of Ascaris suum antigen with both immediate and late increases in airflow resistance (late response). The mechanism of the late response is unknown but recent evidence suggests that the initial generation of slow-reacting substance of anaphylaxis (SRS-A) immediately after antigen challenge is a necessary pre-requisite for the physiologic expression of this late response. Based on this evidence we hypothesized that airway challenge with leukotriene D4 (LTD4), an active component of SRS-A would produce acute and late airway responses in allergic sheep similar to those observed with antigen. In five allergic sheep with documented early and late pulmonary responses to Ascaris suum antigen, inhalation of leukotriene D4 aerosol (delivered dose [mean ± SE] 0.55 ± 0.08 ug) resulted in significant early and late increases in specific lung resistance [SR(L)]. In three allergic sheep which only demonstrated acute responses to antigen, LTD4 aerosol (delivered dose 0.59 ± 0.09 ug) only produced an acute increase in SR(L). In the late responders pretreatment with aerosol cromolyn sodium (1 mg/kg) did not affect the acute response but blunted the late increase in SR(L). Pretreatment with aerosol FPL-57231 (1% w/v solution) completely blocked both the acute and late responses. These data support the hypothesis that initial release of LTD4 in the airways of sensitive animals is important for the physiologic expression of the late response.

Original languageEnglish (US)
Pages (from-to)715-726
Number of pages12
JournalProstaglandins
Volume29
Issue number5
DOIs
StatePublished - May 1985

Keywords

  • Late responses
  • asthma
  • bronchoconstriction
  • leukotriene D
  • sheep

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

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