Asthma is a chronic obstructive pulmonary disease (COPD) which affects 1 in every 12 Americans. Symptoms common to asthmatics include dyspnea, increased mucous production and airway hyperresponsiveness. While research over the past few decades has mostly established the immunological basis behind asthma, there have not been radical changes in the treatment modalities. It is believed that in many COPDs, alveolar macrophages play a critical role in disease progression. While evolutionarily, alveolar macrophages played a significant part in protecting the individual from harmful allergens, in asthma there may be an inappropriate activation of the alveolar macrophages to proteases such as cockroach allergen (CRA). Studies show that children living in inner cities with cockroach infestation are more likely to develop asthma than those that reside in rural areas with less exposure to cockroach allergens. In exposed individuals, when the alveolar macrophages come in contact with CRA, an immune cascade is initiated which sensitizes the child. Subsequent exposure to such an antigen will induce asthma like symptoms. One possible way of reducing such a response is to reduce the number of alveolar macrophages thus avoiding the pathalogical effects. Clodronate liposomes are liposomes that are encapsulated with bisphosphonate clodronate. When a macrophage phagocytoses such a liposome, the result is cellular suicide or apoptosis. In this study, we sensitized a murine model of CRA asthma and then monitored the impact of depleted alveolar macrophages using intratracheal administration of clodronate liposomes. We then studied the effect of this depletion on the recruitment of inflammatory cells such as neutrophils and eosinophils which are primary cellular contributors to the asthmatic response. Our studies show that while clodronate liposomes are effective in alveolar macrophage depletion, the subsequent inflammation through neutrophil recruitment interferes with the study of the delicate milieu of cells in the respiratory epithelium of this murine model.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/13304 |
| Date | 24 September 2015 |
| Creators | Kottapalli, Sai M. |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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