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PAF-acether and experimental anaphylaxis as a model for asthma.
M Pretolani1, A Lellouch-Tubiana, J Lefort
1Unité de Pharmacologie Cellulaire, Unité Associée Institut Pasteur/INSERM No. 285, Paris, France.
International Archives of Allergy and Applied Immunology
|January 1, 1989
Summary
Platelet-activating factor (PAF-acether) plays a key role in hypersensitivity reactions like asthma. PAF-acether triggers asthma symptoms and airway hyperresponsiveness in animal models and humans.
Area of Science:
- Immunology
- Pulmonology
- Pharmacology
Background:
- Platelet-activating factor (PAF-acether) is implicated in hypersensitivity reactions.
- PAF-acether mimics asthma features, causing bronchoconstriction, hypotension, and hemoconcentration.
- It activates platelets and leukocytes, promoting eosinophil migration in the lungs.
Purpose of the Study:
- To investigate the role of PAF-acether in hypersensitivity and asthma.
- To examine PAF-acether's effects on airway hyperresponsiveness in sensitized animals and humans.
- To explore cellular mechanisms underlying PAF-acether-induced hyperresponsiveness.
Main Methods:
- In vivo and in vitro studies using animal models (guinea pigs) and human subjects.
- Administration of PAF-acether and antigens to induce hypersensitivity reactions.
- Measurement of bronchoconstriction, hypotension, hemoconcentration, and inflammatory cell activity.
- Assessment of in vitro bronchopulmonary hyperresponsiveness in sensitized versus non-sensitized lungs.
- Analysis of cyclic adenosine monophosphate (cAMP) levels in alveolar macrophages.
Main Results:
- PAF-acether reproduces key features of asthma, including bronchoconstriction and hypotension.
- Intradermal PAF-acether causes enhanced eosinophil degranulation in atopic individuals.
- PAF-acether induces significant bronchopulmonary hyperresponsiveness in animal models and humans.
- Sensitized guinea pig lungs show increased in vitro hyperresponsiveness to PAF-acether.
- Alveolar macrophages from sensitized animals exhibit reduced cAMP response to prostaglandin E2 and salbutamol.
Conclusions:
- PAF-acether is a critical mediator in hypersensitivity reactions and asthma pathogenesis.
- PAF-acether-induced airway hyperresponsiveness may involve inflammatory cell infiltration or altered resident lung cell reactivity.
- Changes in alveolar macrophage function, specifically cAMP signaling, might contribute to PAF-acether-induced hyperresponsiveness in sensitized lungs.