EFFECTS OF THE BEIGE MUTATION ON RESPIRATORY-TRACT INFECTION WITH PSEUDOMONAS-AERUGINOSA IN MICE

The role of neutrophil proteinases in the pathogenesis of respiratory tract infections with Pseudomonas aeruginosa was evaluated by studying the course of murine respiratory tract infection with a clinical isolate of P. aeruginosa mucoid strain developed by the agarose beads method in C57BL/6J(bg/bg) mice (beige mice). Neutrophils of beige mice are known to have defects in elastase and cathepsin G, but to have normal ability to produce reactive oxygen species. Contrary to the reported high susceptibility of beige mice to bacterial infections, we found that intratracheal inoculation of approximately 10(5) colony-forming units (CFU) of P. aeruginosa enmeshed in agarose beads resulted in lower mortality (0/16 versus 16/16, p < .01), fewer CFU counts in the lungs on day 5 (p < .O5), and fewer elastolytic lung tissue injuries in beige mice compared with C57BL/6(+/+) mice. In vitro bactericidal study, however, revealed that beige neutrophils killed fewer bacteria than those of C57BL/6(+/+) mice (p < .05). Neutrophil elastase activities in the supernatants of pulmonary lavaged fluids measured using methoxysuccinyl-alanyl-alanyl-prolyl-valine-4-methylcoumar- 7-amide were lower (p < .05) in beige mice than those in the normal littermates, whereas neutrophil recruitment into the airways and production of superoxide anion measured as the superoxide dismutase inhibitable rate of cytochrome c reduction were not impaired. These results suggest that neutrophil proteinases play a Key role in tissue injuries in the respiratory tract infection with P. aeruginosa.