Platelet-activating factor (PAF) and PAF antagonists in asthma.

Area of Science:

• Immunology
• Pulmonology
• Pharmacology

Background:

• Platelet-activating factor (PAF) is implicated in immediate hypersensitivity and anaphylaxis.
• PAF activates inflammatory cells like monocytes, mast cells, and platelets.
• PAF's role in conditions like asthma is under investigation.

Purpose of the Study:

• To investigate the role of PAF in immediate hypersensitivity and allergic lung responses.
• To understand the mechanisms behind enhanced lung responsiveness in sensitized animals.
• To explore potential cellular defects contributing to allergic bronchoconstriction.

Main Methods:

• Studied PAF's effect on cyclic AMP levels in guinea-pig alveolar cells.
• Assessed the in vivo activity of PAF antagonists in normal and actively sensitized guinea-pigs.
• Analyzed mediator-induced bronchoconstriction and inflammatory cell recruitment in sensitized lungs.

Main Results:

• PAF reduces cyclic AMP levels, supporting its role in mediator release.
• PAF antagonists showed reduced efficacy in actively sensitized guinea-pig lungs.
• Sensitized lungs exhibited hyper-responsiveness to PAF, LTD4, histamine, and arachidonic acid.
• Recruitment of peripheral inflammatory cells into the lungs of sensitized animals was observed.
• Alveolar cells from sensitized animals showed reduced responsiveness to cyclic AMP-stimulating agents.

Conclusions:

• Actively sensitized lungs are hyper-responsive to mediators, potentially due to recruited inflammatory cells.
• A cellular defect may exist in sensitized lungs, contributing to allergen-induced bronchoconstriction and cell recruitment.
• A 'pre-inflamed' lung state in sensitized animals and asthmatics may precede and facilitate allergic responses.