PAF-induced airway responses in sheep: Effects of a PAF antagonist and nedocromil sodium

M. Soler, E. Mansour, A. Fernandez, J. D'Brot, T. Ahmed, W. M. Abraham

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Platelet-activating factor (PAF) is a potent inflammatory mediator that can cause bronchoconstriction and airway hyperresponsiveness in selected human subjects and animals. The mechanism by which PAF induces these changes is not clearly understood. We therefore studied the effects of intratracheal instillation of PAF (30 μg/kg) on airway resistance and airway responsiveness in allergic sheep (n = 7) and attempted to modulate these effects with the specific PAF antagonist, WEB-2086, and the antiasthmatic agent, nedocromil sodium (NED). Specific lung resistance (SRL) was measured to assess bronchial responses to PAF, and airway responsiveness was determined by deriving a provocative dose of carbachol in breath units causing an increase in SRL to 4 L times centimeters of H2O per liters per second (PD4) from carbachol dose-response curves. PAF instillation increased mean ± SD SRL to 228 ± 134% above baseline. Two to 4 hours after PAF instillation, PD4 decreased by 55 ± 9% from a baseline of 39 ± 9 breath units (p < 0.05). Airway responsiveness remained increased at 24 hours but returned to baseline by 48 hours. Pretreatment with WEB-2086 (3 mg/kg, intravenously) or NED (1 mg/kg, nebulized) blocked (p < 0.05,) PAF-induced bronchoconstriction and PAF-induced airway hyperresponsiveness. Instillation of lyso-PAF (30 μg/kg) did not cause bronchoconstriction or airway hyperresponsiveness. Thus, instilled PAF causes bronchoconstriction and airway hyperresponsiveness in allergic sheep by a receptor-mediated mechanism that likely involves the release of secondary mediators, the latter process being sensitive to NED.

Original languageEnglish (US)
Pages (from-to)661-668
Number of pages8
JournalThe Journal of Allergy and Clinical Immunology
Volume85
Issue number3
DOIs
StatePublished - Mar 1990

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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