Synergism of Pseudomonas aeruginosa exotoxin A with endotoxin, superantigen, or TNF results in TNFR1- and TNFR2-dependent liver toxicity in mice.
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Synergism of Pseudomonas aeruginosa exotoxin A with endotoxin, superantigen, or TNF results in TNFR1- and TNFR2-dependent liver toxicity in mice. / Schümann, J; Bluethmann, H; Tiegs, Gisa.
In: IMMUNOL LETT, Vol. 74, No. 2, 2, 2000, p. 165-172.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Synergism of Pseudomonas aeruginosa exotoxin A with endotoxin, superantigen, or TNF results in TNFR1- and TNFR2-dependent liver toxicity in mice.
AU - Schümann, J
AU - Bluethmann, H
AU - Tiegs, Gisa
PY - 2000
Y1 - 2000
N2 - Pseudomonas aeruginosa is a potentially dangerous Gram-negative nosocomial pathogen, causing bacteremia in debilitated patients, and a prominent cause of bacterial cholangitis. Opportunistic infections with other nosocomial pathogens, e.g. Staphylococcus aureus, are common. Hence, multi-intoxication with P. aeruginosa exotoxin A (PEA) and other bacterial toxins, including endotoxin (LPS) and the superantigen S. aureus enterotoxin B (SEB), is very likely. Here we show that PEA synergistically interacted with LPS, SEB, or recombinant murine tumor necrosis factor alpha (rmuTNF) in mice, resulting in severe liver injury. Enhanced and prolonged circulation of cytokines, including TNF, which depended on the presence of T cells, was a remarkable feature of synergistic PEA/LPS- or PEA/SEB-induced hepatotoxicity. PEA/LPS-, PEA/SEB- or PEA/rmuTNF-induced liver injury was mediated by both TNF receptors (TNFRs), i.e. TNFR1 and TNFR2. In view of the fact that TNFR1, but not TNFR2, signaling is unequivocally required for host defense, our results suggest that anti-TNFR2 strategies might be beneficial to protect the liver from inflammatory damage caused by synergistic interactions of PEA with other TNF-inducing bacterial toxins.
AB - Pseudomonas aeruginosa is a potentially dangerous Gram-negative nosocomial pathogen, causing bacteremia in debilitated patients, and a prominent cause of bacterial cholangitis. Opportunistic infections with other nosocomial pathogens, e.g. Staphylococcus aureus, are common. Hence, multi-intoxication with P. aeruginosa exotoxin A (PEA) and other bacterial toxins, including endotoxin (LPS) and the superantigen S. aureus enterotoxin B (SEB), is very likely. Here we show that PEA synergistically interacted with LPS, SEB, or recombinant murine tumor necrosis factor alpha (rmuTNF) in mice, resulting in severe liver injury. Enhanced and prolonged circulation of cytokines, including TNF, which depended on the presence of T cells, was a remarkable feature of synergistic PEA/LPS- or PEA/SEB-induced hepatotoxicity. PEA/LPS-, PEA/SEB- or PEA/rmuTNF-induced liver injury was mediated by both TNF receptors (TNFRs), i.e. TNFR1 and TNFR2. In view of the fact that TNFR1, but not TNFR2, signaling is unequivocally required for host defense, our results suggest that anti-TNFR2 strategies might be beneficial to protect the liver from inflammatory damage caused by synergistic interactions of PEA with other TNF-inducing bacterial toxins.
KW - Animals
KW - Mice
KW - Mice, Inbred BALB C
KW - Mice, Inbred C57BL
KW - Mice, Mutant Strains
KW - ADP Ribose Transferases
KW - Bacterial Toxins
KW - Cytokines/blood
KW - Virulence Factors
KW - Alanine Transaminase/blood
KW - Antibodies, Monoclonal/pharmacology
KW - Antigens, Thy-1/immunology
KW - DNA Fragmentation
KW - Drug-Induced Liver Injury/metabolism
KW - Exotoxins/pharmacology
KW - Lipopolysaccharides/pharmacology
KW - Receptors, Tumor Necrosis Factor/genetics/physiology
KW - Staphylococcus aureus/immunology
KW - Superantigens/pharmacology
KW - T-Lymphocytes/drug effects
KW - Tumor Necrosis Factor-alpha/pharmacology
KW - Animals
KW - Mice
KW - Mice, Inbred BALB C
KW - Mice, Inbred C57BL
KW - Mice, Mutant Strains
KW - ADP Ribose Transferases
KW - Bacterial Toxins
KW - Cytokines/blood
KW - Virulence Factors
KW - Alanine Transaminase/blood
KW - Antibodies, Monoclonal/pharmacology
KW - Antigens, Thy-1/immunology
KW - DNA Fragmentation
KW - Drug-Induced Liver Injury/metabolism
KW - Exotoxins/pharmacology
KW - Lipopolysaccharides/pharmacology
KW - Receptors, Tumor Necrosis Factor/genetics/physiology
KW - Staphylococcus aureus/immunology
KW - Superantigens/pharmacology
KW - T-Lymphocytes/drug effects
KW - Tumor Necrosis Factor-alpha/pharmacology
M3 - SCORING: Journal article
VL - 74
SP - 165
EP - 172
JO - IMMUNOL LETT
JF - IMMUNOL LETT
SN - 0165-2478
IS - 2
M1 - 2
ER -
