K P Leong1, D P Huston. 1. Department of Rheumatology and Immunology, Tan Tock Seng Hospital, Singapore. khai_pang_leong@notes.ttsh.gov.sg
Abstract
OBJECTIVE: This paper reviews the current views of the pathogenesis of airway eosinophilic inflammation and airway hyperresponsiveness (AHR) in allergic asthma based on mouse models of the disease. The reader will also encounter new treatment strategies that have arisen as this knowledge is applied in practice. DATA SOURCES: MEDLINE searches were conducted with key words asthma, mouse model, and murine. Additional articles were identified from references in articles and book chapters. STUDY SELECTION: Original research papers and review articles from peer-reviewed journals were chosen. RESULTS: Although the mouse model does not replicate human asthma exactly, the lessons learned about the pathogenesis of allergic airway inflammation and AHR are generally applicable in humans. Type 2 T helper lymphocytes (Th2) orchestrate the inflammation and are crucial for the development of AHR. Cells and molecules involved in T cell activation (dendritic cells, T cell receptor, major histocompatibility complex molecule, and costimulatory molecules) are also vital. Besides these, no other cell or molecule could be shown to be indispensable for the establishment of the model under all experimental conditions. There are at least three pathways that lead to AHR. One is dependent on immunoglobulin E and mast cells, one on eosinophils and interleukin-5 (IL-5), and one on IL-13. Eosinophils are probably the most important effector cells of AHR. Radical methods to treat asthma have been tested in the animal model, including modifying the polarity of lymphocyte response and antagonizing IL-5. CONCLUSIONS: AHR, the hallmark of asthma, is attributable to airway inflammation ultimately mediated by helper T cells via three pathways, at least. The mouse model is also a valuable testing ground for new therapies of asthma.
OBJECTIVE: This paper reviews the current views of the pathogenesis of airway eosinophilic inflammation and airway hyperresponsiveness (AHR) in allergic asthma based on mouse models of the disease. The reader will also encounter new treatment strategies that have arisen as this knowledge is applied in practice. DATA SOURCES: MEDLINE searches were conducted with key words asthma, mouse model, and murine. Additional articles were identified from references in articles and book chapters. STUDY SELECTION: Original research papers and review articles from peer-reviewed journals were chosen. RESULTS: Although the mouse model does not replicate humanasthma exactly, the lessons learned about the pathogenesis of allergic airway inflammation and AHR are generally applicable in humans. Type 2 T helper lymphocytes (Th2) orchestrate the inflammation and are crucial for the development of AHR. Cells and molecules involved in T cell activation (dendritic cells, T cell receptor, major histocompatibility complex molecule, and costimulatory molecules) are also vital. Besides these, no other cell or molecule could be shown to be indispensable for the establishment of the model under all experimental conditions. There are at least three pathways that lead to AHR. One is dependent on immunoglobulin E and mast cells, one on eosinophils and interleukin-5 (IL-5), and one on IL-13. Eosinophils are probably the most important effector cells of AHR. Radical methods to treat asthma have been tested in the animal model, including modifying the polarity of lymphocyte response and antagonizing IL-5. CONCLUSIONS: AHR, the hallmark of asthma, is attributable to airway inflammation ultimately mediated by helper T cells via three pathways, at least. The mouse model is also a valuable testing ground for new therapies of asthma.
Authors: Julia K L Walker; Alan M Fong; Barbara L Lawson; Jordan D Savov; Dhavalkumar D Patel; David A Schwartz; Robert J Lefkowitz Journal: J Clin Invest Date: 2003-08 Impact factor: 14.808