Mechanism of platelet activating factor-induced bronchoconstriction in humans

Lewis J Smith, A. H.E. Rubin, R. Patterson

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

The inhalation of platelet activating factor (PAF) produces bronchoconstriction in normal and asthmatic subjects. To identify the mechanism by which PAF-induced bronchoconstriction occurs in humans, bronchoprovocation testing was performed in 7 subjects (3 normal, 4 with mild asthma) after pretreatment with phosphate-buffered saline (PBS), atropine, chlorpheniramine, or indomethacin. We determined the nebulizer concentration of PAF which reduced specific airway conductance (SGaw) 35% (PC35 SGaw) and the slope of the PAF dose-response curve. Atropine produced baseline bronchodilatation (SGaw increased 50%), while chlorpheniramine and indomethacin had no effect on baseline pulmonary function. Atropine increased airway responsiveness to PAF: the PC35 SGaw decreased 40% (p < 0.05) and the slope of the PAF dose-response curve increased 86% (p < 0.05). In contrast, chlorpheniramine inhibited the airway response to PAF: the PC35 SGaw increased 87% (p < 0.05), while the slope of the PAF dose-response curve decreased an insignificant 37%. Indomethacin did not affect either measurement. Chlorpheniramine also prevented the PAF-induced facial flushing and feeling of warmth; atropine and indomethacin did not. These results suggest that PAF-induced bronchoconstriction in humans is mediated at least in part by histamine release, not by cholinergic or cyclooxygenase-dependent mechanisms. Other indirect effects, such as the release of sulfidopeptide leukotrienes, or a direct effect on airway smooth muscle may also contribute to PAF-induced bronchoconstriction. Why atropine heightened the airway response to PAF is unclear.

Original languageEnglish (US)
Pages (from-to)1015-1019
Number of pages5
JournalAmerican Review of Respiratory Disease
Volume137
Issue number5
DOIs
StatePublished - Jan 1 1988

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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