Importance of Kupffer cells for T-cell-dependent liver injury in mice.
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Importance of Kupffer cells for T-cell-dependent liver injury in mice. / Schümann, J; Wolf, D; Pahl, A; Brune, K; Papadopoulos, T; van Rooijen, N; Tiegs, Gisa.
In: AM J PATHOL, Vol. 157, No. 5, 5, 2000, p. 1671-1683.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Importance of Kupffer cells for T-cell-dependent liver injury in mice.
AU - Schümann, J
AU - Wolf, D
AU - Pahl, A
AU - Brune, K
AU - Papadopoulos, T
AU - van Rooijen, N
AU - Tiegs, Gisa
PY - 2000
Y1 - 2000
N2 - T cells seem to be responsible for liver damage in any type of acute hepatitis. Nevertheless, the importance of Kupffer cells (KCs) for T-cell-dependent liver failure is unclear. Here we focus on the role of KCs and tumor necrosis factor (TNF) production after T cell stimulation in mice. T-cell- and TNF-dependent liver injury were induced either by Pseudomonas exotoxin A (PEA), by concanavalin A (Con A), or by the combination of subtoxic doses of PEA and the superantigen Staphylococcus enterotoxin B (SEB). KCs were depleted by clodronate liposomes. Although livers of PEA-treated mice contained foci of confluent necrosis and numerous apoptotic cells, hardly any apoptotic cells were observed in the livers of Con A-treated mice. Instead, large bridging necroses were visible. Elimination of KCs protected mice from PEA-, Con A-, or PEA/SEB-induced liver injury. In the absence of KCs, liver damage was restricted to a few small necrotic areas. KCs were the main source of TNF. Hepatic TNF mRNA and protein production were strongly attenuated because of KC-depletion whereas plasma TNF levels were unaltered. Our results suggest that KCs play an important role in T cell activation-induced liver injury by contributing TNF. Plasma TNF levels are poor diagnostic markers for the severity of TNF-dependent liver inflammation.
AB - T cells seem to be responsible for liver damage in any type of acute hepatitis. Nevertheless, the importance of Kupffer cells (KCs) for T-cell-dependent liver failure is unclear. Here we focus on the role of KCs and tumor necrosis factor (TNF) production after T cell stimulation in mice. T-cell- and TNF-dependent liver injury were induced either by Pseudomonas exotoxin A (PEA), by concanavalin A (Con A), or by the combination of subtoxic doses of PEA and the superantigen Staphylococcus enterotoxin B (SEB). KCs were depleted by clodronate liposomes. Although livers of PEA-treated mice contained foci of confluent necrosis and numerous apoptotic cells, hardly any apoptotic cells were observed in the livers of Con A-treated mice. Instead, large bridging necroses were visible. Elimination of KCs protected mice from PEA-, Con A-, or PEA/SEB-induced liver injury. In the absence of KCs, liver damage was restricted to a few small necrotic areas. KCs were the main source of TNF. Hepatic TNF mRNA and protein production were strongly attenuated because of KC-depletion whereas plasma TNF levels were unaltered. Our results suggest that KCs play an important role in T cell activation-induced liver injury by contributing TNF. Plasma TNF levels are poor diagnostic markers for the severity of TNF-dependent liver inflammation.
KW - Animals
KW - Male
KW - Mice
KW - Mice, Inbred BALB C
KW - Drug Combinations
KW - Concanavalin A
KW - Drug-Induced Liver Injury
KW - Tumor Necrosis Factor-alpha/biosynthesis
KW - ADP Ribose Transferases
KW - Bacterial Toxins
KW - Liver/pathology
KW - Virulence Factors
KW - Antigens, Bacterial
KW - Enterotoxins
KW - Exotoxins
KW - Kupffer Cells/physiology
KW - Liver Diseases/etiology/metabolism/pathology
KW - Necrosis
KW - T-Lymphocytes/physiology
KW - Animals
KW - Male
KW - Mice
KW - Mice, Inbred BALB C
KW - Drug Combinations
KW - Concanavalin A
KW - Drug-Induced Liver Injury
KW - Tumor Necrosis Factor-alpha/biosynthesis
KW - ADP Ribose Transferases
KW - Bacterial Toxins
KW - Liver/pathology
KW - Virulence Factors
KW - Antigens, Bacterial
KW - Enterotoxins
KW - Exotoxins
KW - Kupffer Cells/physiology
KW - Liver Diseases/etiology/metabolism/pathology
KW - Necrosis
KW - T-Lymphocytes/physiology
M3 - SCORING: Journal article
VL - 157
SP - 1671
EP - 1683
JO - AM J PATHOL
JF - AM J PATHOL
SN - 0002-9440
IS - 5
M1 - 5
ER -
