Role of Alveolar Macrophages in the Neutrophil-dependent Defense System againstPseudomonas aeruginosaInfection in the Lower Respiratory Tract: Amplifying Effect of Muramyl Dipeptide Analog

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Abstract
Alveolar macrophages are thought to be important in immune or inflammatory reactions. We investigated the role of alveolar macrophages in defense against P. aeruginosa infection in the lower respiratory tract. Intrathecal inoculation of formalin-inactivated P. aeruginosa (1 .times. 104 - 1 .times. 1010 organisms) into normal rats resulted in increase in the number of neutrophils in the bronchoalveolar lavage (BAL) fluid obtained 24 h later. The phagocytic activity of neutrophils for P. aeruginosa was higher than that of alveolar macrophages. These findings indicate that neutrophils are essential for phagocytosis of P. aeruginosa in the lower respiratory tract. On incubation with P. aeruginosa, alveolar macrophages released neutrophil chemotactic factor (NCF) dose-dependently. MDP-Lys(L18), a muramyl dipeptide analog, stimulated alveolar macrophages to phagocytize P. aeruginosa and stimulate the release of NCF from alveolar macrophages in vitro and enhanced the neutrophil response to inoculated P. aeruginosa in vivo. These results indicate that alveolar macrophages are important in intiating the neutrophil-dependent defense system against P. aeruginosa by releasing NCF and that NDP-Lys(L18) can amplify the defense system.