Virulence factors from Pseudomonas aeruginosa increase lung epithelial permeability

Pseudomonas aeruginosa infection frequently complicates lung injury and can be fatal in immunocompromised or debilitated individuals. Previous studies from our laboratory indicate that elastase from P, aeruginosa increases ep ithelial permeability by disrupting tight junctions between epithelial cell s. Because the inflammatory reaction of the host is a prominent feature of bacterial infection, we reasoned that additional virulence factors from thi s organism could extend and augment the initial pulmonary injury by prompti ng accumulation of neutrophils. To test this hypothesis, we compared respon ses of guinea pigs to aerosols of elastase (PE) and lipopolysaccharide (LPS ) from P. aeruginosa. After each treatment, we measured epithelial permeabi lity and accumulation of neutrophils, interleukin 8 (IL-8), and beta -glucu ronidase in epithelial lining fluid (ELF). We found that PE increased epith elial permeability, as measured by both the clearance of aerosolized radiol abeled albumin from the air spaces and the concentration of plasma albumin in epithelial lining fluid, but it was less effective than LPS at recruitin g neutrophils into the lungs. In contrast, LPS had no significant effect on epithelium, but it increased the concentration of neutrophils, IL-8, and b eta -glucuronidase in ELF. Increased epithelial permeability induced by PE does not cause lung inflammation, but it may facilitate the LPS-induced inf lux of neutrophils.