A possible role for PAF in allergen-induced late responses

Modification by a selective antagonist

W. M. Abraham, J. S. Stevenson, R. Garrido

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

We determined whether platelet-activating factor (PAF) plays a role in allergen-induced airway responses by studying the effects of a selective PAF antagonist WEB-2086 on antigen-induced early and late airway responses in allergic sheep. In seven sheep, inhaled Ascaris suum produced significant early (282%) and late (176%) increases in specific lung resistance (sRL). WEB-2086 (1 mg/kg iv) given 20 min before antigen challenge did not affect the early response, but the peak late increase in sRL was only 37% over base line (P < 0.05 vs. control). To study the mechanism by which PAF contributes to antigen-induced responses, we evaluated the effects of pharmacological probes on PAF-induced bronchoconstriction. Inhaled PAF (dose range 75-700 μg) caused reproducible (r = 0.781, P < 0.05) increases in sRL in eight sheep. The PAF-induced bronchoconstriction was blocked by WEB-2086 (1 mg/kg iv) and by the leukotriene antagonist FPL-55712 (30 mg by aerosol); however, neither the cyclooxygenase blocker indomethacin (2 mg/kg iv) nor the histamine H1-antagonist chlorpheniramine (2 mg/kg iv) blocked the PAF response. WEB-2086, however, did not block bronchoconstriction induced by aerosol leukotriene D4, indicating that PAF acts indirectly through leukotrienes. Finally, we determined whether PAF could induce late airway responses. Inhaled PAF produced an immediate increase in sRL in all seven sheep tested, but late airway responses were observed in only three of the seven sheep. Our observations show that PAF may play a role in allergen-induced late responses in allergic sheep and that a large component of the PAF-induced response is mediated via spasmogenic leukotrienes. These results support the possibility of sequential mediator activation in vivo.

Original languageEnglish
Pages (from-to)2351-2357
Number of pages7
JournalJournal of Applied Physiology
Volume66
Issue number5
StatePublished - Jan 1 1989
Externally publishedYes

Fingerprint

Platelet Activating Factor
Allergens
WEB 2086
Sheep
Bronchoconstriction
Leukotrienes
Aerosols
Antigens
Histamine H1 Antagonists
Chlorpheniramine
Ascaris suum
Leukotriene D4
Leukotriene Antagonists
Prostaglandin-Endoperoxide Synthases
Indomethacin
Pharmacology

ASJC Scopus subject areas

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

Cite this

A possible role for PAF in allergen-induced late responses : Modification by a selective antagonist. / Abraham, W. M.; Stevenson, J. S.; Garrido, R.

In: Journal of Applied Physiology, Vol. 66, No. 5, 01.01.1989, p. 2351-2357.

Research output: Contribution to journalArticle

Abraham, W. M. ; Stevenson, J. S. ; Garrido, R. / A possible role for PAF in allergen-induced late responses : Modification by a selective antagonist. In: Journal of Applied Physiology. 1989 ; Vol. 66, No. 5. pp. 2351-2357.
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