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[Animal models of bronchial hyperreactivity]
1Le Réseau des Centres d'Excellences en Santé Respiratoire, Laboratoires, Meakins-Christie, Hôpital Royal Victoria, Université McGill, Montréal (Québec) Canada.
Revue Des Maladies Respiratoires
|January 1, 1994
Summary
Animal models like guinea pigs and dogs help study airway hyperresponsiveness, a key feature of asthma. Challenges reveal mechanisms of airway narrowing and inflammation, offering insights into disease pathology.
Area of Science:
- Pulmonary Medicine
- Immunology
- Pharmacology
Background:
- Airway responsiveness is elevated in various airway diseases, notably asthma.
- Animal models are crucial for understanding the mechanisms behind enhanced airway responsiveness.
- Guinea pigs and Basenji-greyhound dogs exhibit airway hyperresponsiveness similar to human asthma.
Purpose of the Study:
- To explore the mechanisms of enhanced airway responsiveness, particularly in the context of asthma.
- To investigate the roles of different agonists and inflammatory mediators in airway narrowing and hyperresponsiveness.
- To characterize the contributions of bronchoconstriction and vascular leak to airway narrowing.
Main Methods:
- Utilizing animal models (guinea pig, Basenji-greyhound dog) to study airway hyperresponsiveness.
- Challenging airways with bronchoconstrictive agonists to induce bronchoconstriction and vascular leak.
- Employing adenosine challenge to assess airway and mast cell responsiveness.
- Investigating indirect airway narrowing induced by bradykinin and tachykinin, likely via leukotriene release.
- Examining enhancement of airway responsiveness through immune and non-immune challenges (ozone, Sephadex, agonists, cytokines).
Main Results:
- Bronchoconstrictive agonist challenge leads to bronchoconstriction and transient vascular leak, both contributing to airway narrowing.
- Adenosine challenge assesses airway responsiveness and effector cell function (e.g., mastocytes).
- Bradykinin and tachykinin induce indirect airway narrowing, potentially through leukotriene liberation.
- Immune and non-immune stimuli, including ozone, Sephadex, agonists (LTD-4, bradykinin, PAF), and cytokines (IL-1, IL-2, TNF-alpha), can enhance airway responsiveness.
- Cyclooxygenase and lipoxygenase products are implicated in these responses.
- Allergen-induced hyperresponsiveness involves airway inflammation, acute roles for bradykinin and platelet-activating factor (PAF), and chronic airway smooth muscle growth.
Conclusions:
- Animal models provide valuable insights into the mechanisms of airway hyperresponsiveness relevant to asthma.
- Both direct (agonist-induced) and indirect pathways contribute to airway narrowing.
- Inflammatory mediators and cellular responses play significant roles in enhanced airway responsiveness.
- Understanding these mechanisms is crucial for developing effective asthma therapies.