UBC Theses and Dissertations
The role of Alveolar macrophages in defense of the lung against Pseudomonas aeruginosa Cheung, Dorothy On Yan
The objective of this study was to evaluate the role of alveolar macrophages (AM) in clearance of Pseudomonas aeruginosa in mice after intrapulmonary challenge. Alveolar macrophages were depleted by intranasal administration of liposome-encapsulated dichloromethylene diphosphonate (LDMDP). Control mice received an equal volume of phosphate buffered saline encapsulated liposomes (LPBS). 24 hours post-instillation of liposomes, a sublethal dose of P. aeruginosa was inoculated intranasally into mice. Lungs, spleen and liver were obtained from the two groups of mice at different time points; viable bacterial counts and histology were then analyzed. 78 - 88 % of alveolar macrophage depletion did not affect the survival rate of infected mice, or clearance of P. aeruginosa from the lung, spleen or liver, as compared to the control group. Recruitment of neutrophils in the lung was similar in both groups. As well, m vitro experiments have shown that freshly explanted alveolar macrophages were not competent to phagocytose unopsonzied P. aeruginosa, but were able to phagoeytose zymosan particles. Further studies were conducted to assess in situ phagocytic activities of alveolar macrophages. Three hours after the intranasal instillation of P. aeruginosa or other particles, bronchoalveolar lavage (BAL) was performed. Alveolar macrophage phagocytosis of zymosan particles (23%) and latex beads (27%) was much higher than that of P. aeruginosa (0-5%). Neutrophils were recruited to the lung in response to a high bacterial dose. These results suggest that the role of alveolar macrophages in the defense of the lung against P. aeruginosa challenge may not extensively involve their phagocytic activities.
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