title: Role of tumor necrosis factor alpha in innate resistance to mouse pulmonary infection with Pseudomonas aeruginosa.
abstract: In the present study, we have investigated the mechanisms underlying mouse resistance to endobronchial infection with Pseudomonas aeruginosa enmeshed in agar beads. This was done by monitoring macrophage activation-associated gene expression in lung and alveolar cells harvested from resistant (BALB/c) and susceptible (DBA/2, C57BL/6, and A/J) strains of mice over the course of infection with P. aeruginosa. Interleukin-1 alpha, interleukin-1 beta, macrophage inflammatory protein-1 alpha, JE, and tumor necrosis factor alpha (TNF-alpha) mRNA expression levels were up-regulated in all strains of mice during the early phase of the infection. The level of TNF-alpha mRNA expression was increased to a greater extent in resistant BALB/c mice than in susceptible DBA/2, C57BL/6, and A/J strains of mice. This observation paralleled a higher secretion of TNF-alpha into the alveolar space of BALB/c mice at 3 and 6 h postinfection. The concentration of TNF-alpha released in alveoli returned to basal levels within 24 h of infection in mice of all strains, even though the TNF-alpha mRNA expression remained high until 3 days after infection. In vivo treatments with either anti-murine TNF-alpha monoclonal antibodies or with aminoguanidine significantly increased the number of P. aeruginosa bacteria detected in the lungs of resistant mice at 3 days postinfection. Overall, these findings indicate that both TNF-alpha and nitric oxide exert a protective role in response to pulmonary infection with P. aeruginosa.
authors.affiliation: McGill Centre for the Study of Host Resistance, Montreal General Hospital Research Institute, Quebec, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Gosselin
authors.forename: J
authors.initials: J
authors.lastname: DeSanctis
authors.forename: M
authors.initials: M
authors.lastname: Boulé
authors.forename: E
authors.initials: E
authors.lastname: Skamene
authors.forename: C
authors.initials: C
authors.lastname: Matouk
authors.forename: D
authors.initials: D
authors.lastname: Radzioch
mesh_terms: D000818:Animals; D001483:Base Sequence; D007113:Immunity, Innate; D008168:Lung / Q000378:metabolism; D008171:Lung Diseases / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000502:physiology; D011552:Pseudomonas Infections / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D013045:Species Specificity; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology*
chemical_list: D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide