SURFACTANT PROTEIN-A-DEFICIENT MICE ARE SUSCEPTIBLE TO PSEUDOMONAS-AERUGINOSA INFECTION

To determine the role of surfactant protein-A (SP-A) in host defense, the murine SP-A locus was targeted by homologous recombination to prod uce mice lacking SP-A. SP-A(-/-) and wild-type mice were infected with mucoid Pseudomonas aeruginosa by intratracheal instillation. Pulmonar y bacterial loads were greater in SP-A-/- than in wild-type mice, with increased numbers of mucoid P, aeruginosa in lung homogenates at 6 an d 24 h after infection. Pulmonary infiltration with polymorphonuclear leukocytes (PMN) was similar in both groups; however, an earlier influ x of PMN into the lung occurred in the SP-A(-/-) mice. The number of b acteria phagocytosed by alveolar macrophages was decreased in the SP-A (-/-) mice at 1 h after infection. Superoxide-radical generation by PM N was similar for the SP-A(-/-) and wild-type mice, but nitrite levels were increased in SP-A(-/-) mice. Concentrations of tumor necrosis fa ctor-alpha, interleukin-6, and macrophage inflammatory protein-2 (proi nflammatory cytokines) were greater in bronchoalveolar lavage fluid at 2 h after infection in SP-A(-/-) mice. SP-A plays an important role i n the pathogenesis of mucoid P. aeruginosa infection in the lung in vi vo by enhancing macrophage phagocytosis and clearance of bacteria, and by modifying the inflammatory response.