Induction of a late asthmatic response associated with airway inflammation in mice

• Published in: European journal of pharmacology 2005-10, Vol.521 (1), p.144-155
• Main Authors: Nabe, Takeshi, Zindl, Carlene L., Jung, Yong Woo, Stephens, Robin, Sakamoto, Akari, Kohno, Shigekatsu, Atkinson, T. Prescott, Chaplin, David D.
• Format: Article
• Language: English
• Subjects: Airway Obstruction - complications; Airway Obstruction - immunology; Airway Obstruction - prevention & control; Airway Resistance - immunology; Alum Compounds - administration & dosage; Animals; Anti-Inflammatory Agents - pharmacology; Asthma; Asthma - etiology; Asthma - immunology; Asthma - prevention & control; Biological and medical sciences; Bronchoalveolar Lavage Fluid - chemistry; Bronchoalveolar Lavage Fluid - cytology; Bronchoalveolar Lavage Fluid - immunology; Chemokine CCL11; Chemokines, CC - analysis; Chronic obstructive pulmonary disease, asthma; Corticosteroid; Cytokine; Cytokines - analysis; Dexamethasone - pharmacology; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Immunoglobulin E - immunology; Immunoglobulin G - immunology; Inflammation; Inflammation - complications; Inflammation - immunology; Inflammation - prevention & control; Injections, Intraperitoneal; Late phase response; Leukocytes - drug effects; Leukocytes - immunology; Lung - immunology; Lung - pathology; Lung - physiopathology; Mast cell; Mast Cells - drug effects; Mast Cells - immunology; Medical sciences; Mice; Mice, Inbred BALB C; Ovalbumin - administration & dosage; Ovalbumin - immunology; Pharmacology. Drug treatments; Pneumology; Proto-Oncogene Proteins c-kit - immunology; Time Factors
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2005.08.015

To investigate mechanisms underlying the late asthmatic response, we developed a murine model using repetitive intratracheal antigen challenge. BALB/c mice sensitized by i.p. injection with ovalbumin + alum were challenged with ovalbumin intratracheally 4 times. The 1st challenge induced early airway obstruction peaking at 30 min but without a late response; however, the 4th challenge caused not only early but also late airway obstruction at 2–8 h. Eosinophils, and CD4 + and CD8 + T lymphocytes were increased in the airway before the 4th but not before the 1st–3rd challenges. The numbers of IgE +/CD117 + (mast) cells were also increased in the lung before the 4th challenge. Levels of Th2 cytokines were also increased in the airway. Daily administration of dexamethasone during the challenge period suppressed all these inflammatory events. Thus, this experimental late asthmatic response is associated with Th2 cytokine production from inflammatory cells recruited as a consequence of the 1st–3rd challenges.