Pulmonary responses to bronchoconstrictor agonists in the mouse

Area of Science:

• Pulmonary Physiology
• Respiratory Medicine
• Immunology

Background:

• Mice are crucial models for studying lung immunology and pathology.
• Previous limitations in measuring pulmonary pathophysiology in live mice hindered research.
• A need existed for methods to assess lung function in mice for disease modeling.

Purpose of the Study:

• To establish the first method for measuring lung function in living, mechanically ventilated mice.
• To characterize the pulmonary responses of mice to various bronchoconstrictor agonists.
• To leverage mouse models for identifying roles of specific cells/mediators in lung inflammation.

Main Methods:

• Developed a method to measure pulmonary conductance (GL) and dynamic compliance (Cdyn) in tracheostomized mice.
• Administered intravenous infusions of methacholine, norepinephrine, serotonin, histamine, and other agonists.
• Assessed changes in GL and Cdyn following agonist administration.

Main Results:

• Successfully measured GL and Cdyn in mice.
• Methacholine, norepinephrine, and serotonin significantly decreased GL and Cdyn.
• Histamine, prostaglandins, leukotrienes, substance P, and platelet-activating factor did not elicit reproducible responses.
• Mouse airway responsiveness patterns resemble those in rats.

Conclusions:

• The developed method enables precise measurement of lung function in mice.
• This technique allows for the characterization of airway responsiveness in mice.
• The mouse model, with its diverse strains, is advantageous for dissecting inflammatory roles in lung diseases like pulmonary anaphylaxis.