Role of Pulmonary Alveolar Macrophages in Defense of the Lung against Pseudomonas aeruginosa

Abstract

ABSTRACT Alveolar macrophages (AM) provide one of the first lines of defense against microbial invasion in the lower airways. The role of AM in the clearance of Pseudomonas aeruginosa in mice after intrapulmonary challenge was evaluated. AM were depleted by intranasal administration of liposome-encapsulated dichloromethylene diphosphonate. At 24 h following the instillation of liposomes, a sublethal dose of P. aeruginosa was inoculated intranasally. Spleen, liver, and lung tissue was then evaluated for viable bacteria and for histopathology. AM depletion of 78 to 88% did not affect the survival rate of infected mice or clearance of P. aeruginosa from the spleen, liver, or lung, compared to the control group, but the mice's susceptibility to Klebsiella pneumoniae was greatly enhanced. The recruitment of neutrophils to the lung was also not affected. Freshly explanted AM were not competent to phagocytose unopsonized P. aeruginosa but were able to phagocytose zymosan particles. Further studies were conducted to assess the in situ phagocytic activities of AM. Three hours after the intranasal instillation of P. aeruginosa or other particles, bronchoalveolar lavage was performed. AM phagocytosis of zymosan particles and latex beads exceeded that of P. aeruginosa . Neutrophils were recruited to the lung in response to a high-dose bacterial challenge. These results suggest that AM do not play an important role in defense of the lung against P. aeruginosa .