Role of alveolar macrophages and neutrophils in the defense system against infection of Pseudomonas aeruginosa in the respiratory tract and the effect of derivative of muramyl dipeptide

Abstract

We investigated the role of alveolar macrophages and neutrophils on the defense system against infection of Pseudomonas aeruginosa (P. aeruginosa) in the lower respiratory tracts of rats. Intratracheal inoculation of formalin-inactivated P. aeruginosa to normal rats showed an increased number of neutrophils in bronchoalveolar lavage (BAL) fluid obtained at 24 hours after the inoculation. This response of neutrophils was induced by intravenous administration of MDP-Lys, which is muramyl dipeptide. Phagocytic activity of neutrophils for P. aeruginosa was higher than that of alveolar macrophages, indicating that neutrophils are essential phagocytes in the defense system against P. aeruginosa infection in the lower respiratory tract. Alveolar macrophages released neutrophil chemotactic factor after phagocytosis of P. aeruginosa. This function of alveolar macrophages was increased by MDP-Lys administration. These results indicated that alveolar macrophages play an important role in neutrophil accumulation by release of neutrophil chemotactic factor after the P. aeruginosa phagocytosis in the lower respiratory tract. Moreover MDP-Lys can amplify the neutrophil-dependent defense system against P. aeruginosa by activation of the alveolar macrophage function in vivo.