Role of broncho-alveolar macrophages in airway eosinophilia in a mouse model of asthma
Date of Completion
Health Sciences, Immunology
Allergic asthma, which afflicts up to 70% of all asthmatics, is characterized by chronic inflammation of the airways, reversible airflow obstruction and airway hyperreactivity. Currently, the etiology and pathophysiology of asthma is not fully understood due to its multifactorial origins and complexity. This research focuses on (1) studying correlation between allergen deposition in the respiratory tract and pulmonary inflammation, and (2) characterizing the role of broncho-alveolar macrophages in airway eosinophilia. It was found that airway eosinophilia is highly correlated with allergen deposition in the lower respiratory tract whereas airway hyperreactivity and systemic immune responses were not. Thus this study suggests that upper and lower respiratory tract might not be as tightly integrated as others have suggested, at least as far as allergen deposition and inflammation is concerned. Based on these observations, it was hypothesized that broncho-alveolar macrophages (BAMs) may be in part responsible for producing inflammatory mediators upon ovalbumin (Ova) challenge in sensitized mice. To test this hypothesis a study was designed to assess differences in gene expression profiles in purified BAMs isolated from sensitized and challenged, sensitized alone or challenged-only control animals. It was found that BAMs express genes relevant to asthma pathophysiology in response to challenge in sensitized mice. Large differences in gene expression identified by microarray were confirmed using real-time PCR and indicated that several interesting families of genes were differentially expressed. For example, BAMs isolated from sensitized/challenged mice expressed many genes associated with alternatively activated macrophages such as chitinase and arginase. Other important chemokine genes were upregulated, supporting the possibility that these cells may participate in the initial recruitment of inflammatory cells from the lung parenchyma to the airway lumen. Taken together, this research supports the notion that BAMs may play an important role in asthma pathophysiology, especially upon repeated antigen exposure in the lower respiratory tract of sensitized animals. ^
Siddiqui, Shafiuddin, "Role of broncho-alveolar macrophages in airway eosinophilia in a mouse model of asthma" (2008). Doctoral Dissertations. AAI3334971.