Late phase bronchial obstruction following nonimmunologic mast cell degranulation

Area of Science:

• Allergy and Immunology
• Respiratory Medicine
• Pharmacology

Background:

• Allergic reactions involve mast cell degranulation, leading to airway obstruction.
• The roles of non-immunologic mast cell degranulation in airway responses are not fully understood.

Purpose of the Study:

• To investigate if non-immunologic mast cell degranulation by compound 48/80 mimics immunologic degranulation effects.
• To determine the mediators involved in compound 48/80-induced airway responses.

Main Methods:

• Allergic sheep inhaled compound 48/80 aerosol.
• Pulmonary function (specific lung resistance, thoracic gas volume) and arterial oxygen tension were measured.
• Sheep were pretreated with mast cell stabilizers, histamine H1-antagonists, or SRS-A antagonists.

Main Results:

• Compound 48/80 induced significant early and late increases in specific lung resistance and decreased oxygen tension.
• These responses were prevented by cromolyn sodium (mast cell stabilizer).
• Histamine H1-antagonist had no effect, while SRS-A antagonist prevented the late response.

Conclusions:

• Non-immunologic mast cell degranulation causes early and late bronchial obstructions in sheep, similar to immunologic stimuli.
• Histamine and SRS-A contribute to the early response.
• Early SRS-A release is critical for the development of the late airway obstruction.