title: Virulence factors from Pseudomonas aeruginosa increase lung epithelial permeability.
abstract: 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 epithelial permeability by disrupting tight junctions between epithelial cells. Because the inflammatory reaction of the host is a prominent feature of bacterial infection, we reasoned that additional virulence factors from this organism could extend and augment the initial pulmonary injury by prompting accumulation of neutrophils. To test this hypothesis, we compared responses of guinea pigs to aerosols of elastase (PE) and lipopolysaccharide (LPS) from P. aeruginosa. After each treatment, we measured epithelial permeability and accumulation of neutrophils, interleukin 8 (IL-8), and beta-glucuronidase in epithelial lining fluid (ELF). We found that PE increased epithelial permeability, as measured by both the clearance of aerosolized radiolabeled albumin from the air spaces and the concentration of plasma albumin in epithelial lining fluid, but it was less effective than LPS at recruiting neutrophils into the lungs. In contrast, LPS had no significant effect on epithelium, but it increased the concentration of neutrophils, IL-8, and beta-glucuronidase in ELF. Increased epithelial permeability induced by PE does not cause lung inflammation, but it may facilitate the LPS-induced influx of neutrophils.
authors.affiliation: Department of Specialty Care Services, University of Texas Health Science Center, Tyler, TX 75708, USA.
authors.forename: A O
authors.initials: AO
authors.lastname: Azghani
authors.forename: E J
authors.initials: EJ
authors.lastname: Miller
authors.forename: B T
authors.initials: BT
authors.lastname: Peterson
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology*; D018893:Bronchoalveolar Lavage; D002463:Cell Membrane Permeability / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005966:Glucuronidase / Q000378:metabolism; D006168:Guinea Pigs; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008666:Metalloendopeptidases / Q000494:pharmacology*; D009504:Neutrophils / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000737:chemistry* / Q000472:pathogenicity; D013668:Technetium Tc 99m Aggregated Albumin / Q000378:metabolism; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D016209:Interleukin-8; D008070:Lipopolysaccharides; D013668:Technetium Tc 99m Aggregated Albumin; D005966:Glucuronidase; D008666:Metalloendopeptidases; C043859:pseudolysin, Pseudomonas aeruginosa