NK cells, but not NKT cells, are involved in Pseudomonas aeruginosa exotoxin A-induced hepatotoxicity in mice.
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NK cells, but not NKT cells, are involved in Pseudomonas aeruginosa exotoxin A-induced hepatotoxicity in mice. / Mühlen, Katrin A; Schümann, Jens; Wittke, Frederick; Stenger, Steffen; Nico, Van Rooijen; Luc, Van Kaer; Tiegs, Gisa.
in: J IMMUNOL, Jahrgang 172, Nr. 5, 5, 2004, S. 3034-3041.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - NK cells, but not NKT cells, are involved in Pseudomonas aeruginosa exotoxin A-induced hepatotoxicity in mice.
AU - Mühlen, Katrin A
AU - Schümann, Jens
AU - Wittke, Frederick
AU - Stenger, Steffen
AU - Nico, Van Rooijen
AU - Luc, Van Kaer
AU - Tiegs, Gisa
PY - 2004
Y1 - 2004
N2 - Pseudomonas aeruginosa exotoxin A (PEA) causes T cell- and Kupffer cell (KC)-dependent liver injury in mice. TNF-alpha as well as IL-18 and perforin are important mediators of liver damage following PEA injection. In this study, we focus on the role of NK and NKT cells in PEA-induced liver toxicity. Depletion of both NK and NKT cells by injection of anti-NK1.1 Ab as well as depletion of NK cells alone by anti-asialo GM1 Ab protected mice from PEA-induced hepatotoxicity, whereas mice lacking only NKT cells were susceptible. Additionally, we observed infiltration of NK cells, T cells, and neutrophils into liver parenchyma after injection of PEA. The number of NKT cells, however, remained unchanged. The increase in intrahepatic NK cells depended on KCs and the TNF-alpha-dependent up-regulation of the adhesion molecule VCAM-1 in the liver, but not on NKT cells. PEA also augmented the cytotoxicity of hepatic NK cells against typical NK target cells (YAC-1 cells). This effect depended on KCs, but not on TNF-alpha or NKT cells. Furthermore, only weak expression of MHC class I was detected on hepatocytes, which was further down-regulated in PEA-treated mice. This could explain the susceptibility of hepatocytes to NK cell cytolytic activity in this model. Our results demonstrate that NK cells, activated and recruited independently of NKT cells, contribute to PEA-induced T cell-dependent liver injury in mice.
AB - Pseudomonas aeruginosa exotoxin A (PEA) causes T cell- and Kupffer cell (KC)-dependent liver injury in mice. TNF-alpha as well as IL-18 and perforin are important mediators of liver damage following PEA injection. In this study, we focus on the role of NK and NKT cells in PEA-induced liver toxicity. Depletion of both NK and NKT cells by injection of anti-NK1.1 Ab as well as depletion of NK cells alone by anti-asialo GM1 Ab protected mice from PEA-induced hepatotoxicity, whereas mice lacking only NKT cells were susceptible. Additionally, we observed infiltration of NK cells, T cells, and neutrophils into liver parenchyma after injection of PEA. The number of NKT cells, however, remained unchanged. The increase in intrahepatic NK cells depended on KCs and the TNF-alpha-dependent up-regulation of the adhesion molecule VCAM-1 in the liver, but not on NKT cells. PEA also augmented the cytotoxicity of hepatic NK cells against typical NK target cells (YAC-1 cells). This effect depended on KCs, but not on TNF-alpha or NKT cells. Furthermore, only weak expression of MHC class I was detected on hepatocytes, which was further down-regulated in PEA-treated mice. This could explain the susceptibility of hepatocytes to NK cell cytolytic activity in this model. Our results demonstrate that NK cells, activated and recruited independently of NKT cells, contribute to PEA-induced T cell-dependent liver injury in mice.
KW - Animals
KW - Male
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Injections, Intravenous
KW - ADP Ribose Transferases/toxicity
KW - Adjuvants, Immunologic/toxicity
KW - Bacterial Toxins/toxicity
KW - Cell Movement/immunology
KW - Cytotoxicity, Immunologic/immunology
KW - Down-Regulation/immunology
KW - Exotoxins/toxicity
KW - Histocompatibility Antigens Class I/biosynthesis
KW - Killer Cells, Natural/immunology/microbiology/pathology
KW - Kupffer Cells/immunology
KW - Liver/immunology/metabolism/microbiology/pathology
KW - Neutrophil Infiltration/immunology
KW - T-Lymphocyte Subsets/immunology/pathology
KW - Tumor Necrosis Factor-alpha/physiology
KW - Up-Regulation/immunology
KW - Vascular Cell Adhesion Molecule-1/biosynthesis
KW - Virulence Factors/toxicity
KW - Animals
KW - Male
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Injections, Intravenous
KW - ADP Ribose Transferases/toxicity
KW - Adjuvants, Immunologic/toxicity
KW - Bacterial Toxins/toxicity
KW - Cell Movement/immunology
KW - Cytotoxicity, Immunologic/immunology
KW - Down-Regulation/immunology
KW - Exotoxins/toxicity
KW - Histocompatibility Antigens Class I/biosynthesis
KW - Killer Cells, Natural/immunology/microbiology/pathology
KW - Kupffer Cells/immunology
KW - Liver/immunology/metabolism/microbiology/pathology
KW - Neutrophil Infiltration/immunology
KW - T-Lymphocyte Subsets/immunology/pathology
KW - Tumor Necrosis Factor-alpha/physiology
KW - Up-Regulation/immunology
KW - Vascular Cell Adhesion Molecule-1/biosynthesis
KW - Virulence Factors/toxicity
M3 - SCORING: Journal article
VL - 172
SP - 3034
EP - 3041
JO - J IMMUNOL
JF - J IMMUNOL
SN - 0022-1767
IS - 5
M1 - 5
ER -
