title: Effect of Pseudomonas aeruginosa exotoxin A on endotoxin-induced tumour necrosis factor production in murine lung.
abstract: The ability of several Pseudomonas aeruginosa exo-enzymes, including exotoxin A (ETA), to induce inflammation and their influence on endotoxin-induced tumour necrosis factor (TNF) production in murine lung were evaluated. Intratracheal administration of lipopolysaccharide (LPS; 0.1-10 microg/mouse), 2(-1) LD50 of P. aeruginosa alkaline protease (7.5 microg/mouse) and elastase (1.2 microg/mouse) elevated total cell number and the percentage of neutrophils in broncho-alveolar lavage fluid (BALF), whereas ETA (0.1 microg/mouse) did not. LPS induced TNF production in BALF in a dose-dependent manner, whereas the P. aeruginosa exo-enzymes did not. When ETA was inoculated into the respiratory tract before LPS, production of TNF in BALF was significantly suppressed in a dose-dependent manner. ETA also suppressed TNF production by alveolar macrophages (AMs) stimulated with LPS in vitro. Flow cytometric analysis showed that ETA markedly reduced the expression of CD14 and CD11c/CD18 on the surface of AMs. ETA also depressed partially the expression of TNF-alpha mRNA in AMs. These findings suggest that ETA regulates TNF production in murine lung by suppressing LPS receptor expression, mRNA expression and protein synthesis and/or secretion of TNF.
authors.affiliation: Departments of Laboratory Medicine, Jichi Medical School, Minamikawachi, Tochigi 329-0498, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Hirakata
authors.affiliation: Departments of Laboratory Medicine, Jichi Medical School, Minamikawachi, Tochigi 329-0498, Japan.
authors.forename: Teruo
authors.initials: T
authors.lastname: Kirikae
authors.affiliation: Departments of Pulmonary Medicine, Jichi Medical School, Minamikawachi, Tochigi 329-0498, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Kirikae
authors.affiliation: Departments of Laboratory Medicine, Jichi Medical School, Minamikawachi, Tochigi 329-0498, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Departments of Laboratory Medicine, Jichi Medical School, Minamikawachi, Tochigi 329-0498, Japan.
authors.forename: Kohichi
authors.initials: K
authors.lastname: Izumikawa
authors.affiliation: Departments of Laboratory Medicine, Jichi Medical School, Minamikawachi, Tochigi 329-0498, Japan.
authors.forename: Hiromu
authors.initials: H
authors.lastname: Takemura
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, 7-1 Sakamotomachi, Nagasaki 852-8501.
authors.forename: Shigefumi
authors.initials: S
authors.lastname: Maesaki
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, 7-1 Sakamotomachi, Nagasaki 852-8501.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Tomono
authors.affiliation: Departments of Laboratory Medicine, Jichi Medical School, Minamikawachi, Tochigi 329-0498, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Departments of Laboratory Medicine, Jichi Medical School, Minamikawachi, Tochigi 329-0498, Japan.
authors.forename: Shimeru
authors.initials: S
authors.lastname: Kamihira
authors.affiliation: Departments of Microbiology, Jichi Medical School, Minamikawachi, Tochigi 329-0498, Japan.
authors.forename: Masayasu
authors.initials: M
authors.lastname: Nakano
authors.affiliation: Departments of Pulmonary Medicine, Jichi Medical School, Minamikawachi, Tochigi 329-0498, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kitamura
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, 7-1 Sakamotomachi, Nagasaki 852-8501.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
mesh_terms: D036002:ADP Ribose Transferases; D000818:Animals; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018821:CD18 Antigens / Q000032:analysis; D015536:Down-Regulation; D005098:Exotoxins / Q000633:toxicity*; D016167:Integrin alphaXbeta2 / Q000032:analysis; D007928:Lethal Dose 50; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides / Q000633:toxicity*; D008168:Lung / Q000187:drug effects*; D016676:Macrophages, Alveolar; D008297:Male; D008666:Metalloendopeptidases / Q000633:toxicity; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D012697:Serine Endopeptidases / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
chemical_list: D036002:ADP Ribose Transferases; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D018821:CD18 Antigens; D005098:Exotoxins; D016167:Integrin alphaXbeta2; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008666:Metalloendopeptidases; D012333:RNA, Messenger; D012697:Serine Endopeptidases; D014409:Tumor Necrosis Factor-alpha; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C038495:Pseudomonas serine proteinase; C043859:pseudolysin, Pseudomonas aeruginosa