Bacterial killing is enhanced by expression of lysozyme in the lungs of transgenic mice

To assess the role of lysozyme in pulmonary host defense in vivo, transgeni c mice expressing rat lysozyme cDNA in distal respiratory epithelial cells were generated. Two transgenic mouse lines were established in which the le vel of lysozyme protein in bronchoalveolar (BAL) lavage fluid was increased 2- or 4-fold relative to that in WT mice, Lung structure and cellular comp osition of BAL were not altered by the expression of lysozyme, Lysozyme act ivity in BAI, was significantly increased (6,6- and 17-fold) in 5-wk-old an imals from each transgenic line. To determine whether killing of bacteria w as enhanced by expression of rat lysozyme, 5-wk-old transgenic mice and WT littermates were infected with 10(6) CFU of group B streptococci or 10(7) C FU of a mucoid strain of Pseudomonas aeruginosa by intratracheal injection, Killing of group B streptococci was significantly enhanced (2- and 3-fold) in the mouse transgenic lines at 6 h postinfection and was accompanied by a decrease In systemic dissemination of pathogen, Killing of Pseudomonas ae ruginosa was also enhanced in the transgenic lines (5- and 30-fold). Twenty -four hours after administration of Pseudomonas aeruginosa, all transgenic mice survived, whereas 20% of the WT mice died, Increased production of lgs ozyme in respiratory epithelial cells of transgenic mice enhanced bacterial killing in the lung in vivo, and was associated with decreased systemic di ssemination of pathogen and increased survival following infection.