PMID- 7806154
OWN - NLM
STAT- MEDLINE
DCOM- 19950201
LR  - 20240109
IS  - 0270-9139 (Print)
IS  - 0270-9139 (Linking)
VI  - 21
IP  - 1
DP  - 1995 Jan
TI  - Concanavalin A-induced T-cell-mediated hepatic injury in mice: the role of tumor 
      necrosis factor.
PG  - 190-8
AB  - Concanavalin A activates T lymphocytes in vitro and causes T-cell-dependent 
      hepatic injury in mice. T lymphocytes were previously identified as effector 
      cells of concanavalin A-induced liver injury. Here we report that hepatic injury 
      is characterized by apoptotic cell death. On concanavalin A challenge, the 
      cytokines tumor necrosis factor-alpha (TNF alpha), interleukin-2, granulocyte 
      macrophage-colony stimulating factor, and interferon-gamma were detectable in the 
      circulation of the mice. Pretreatment of mice with anti-mouse TNF-alpha antiserum 
      protected them from concanavalin A-induced liver injury. Nude mice failed to 
      release TNF-alpha or interleukin-2 after concanavalin A challenge and were 
      protected from liver injury. Lymph node cell transfer from responder mice to 
      resistant nude mice resulted in susceptibility of the latter towards concanavalin 
      A, i.e., to induction of cytokine release and hepatotoxicity. These experiments 
      suggest that immunocompetent T cells play a pivotal role in concanavalin 
      A-stimulated TNF-alpha release in vivo. After intravenous administration of 
      fluorescein isothiocyanate-labeled concanavalin A to mice, the most fluorescence 
      was found within the liver. In vitro, concanavalin A stimulation of separate 
      cultures of mouse lymph node cells or nonparenchymal liver cells induced the 
      release of minute amounts of TNF, whereas stimulation of cocultures of these 
      cells resulted in production of substantial amounts of TNF-alpha. These findings 
      may explain the hepatotropic effect of concanavalin A. In conclusion, 
      T-cell-dependent concanavalin A-induced apoptotic liver injury in mice is related 
      to immunological and cytokine-mediated disorders and possibly to autoreactive 
      hepatic processes.
FAU - Gantner, F
AU  - Gantner F
AD  - Faculty of Biology, University of Konstanz, Germany.
FAU - Leist, M
AU  - Leist M
FAU - Lohse, A W
AU  - Lohse AW
FAU - Germann, P G
AU  - Germann PG
FAU - Tiegs, G
AU  - Tiegs G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (Immune Sera)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 11028-71-0 (Concanavalin A)
RN  - I223NX31W9 (Fluorescein-5-isothiocyanate)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Cells, Cultured
MH  - Concanavalin A/antagonists & inhibitors/*pharmacology
MH  - Fluorescein-5-isothiocyanate
MH  - Immune Sera/immunology/pharmacology
MH  - Immunocompetence
MH  - Liver/*drug effects/metabolism/pathology
MH  - Lymph Nodes/cytology/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Mice, Nude
MH  - T-Lymphocytes/immunology/*physiology
MH  - Time Factors
MH  - Tumor Necrosis Factor-alpha/immunology/*physiology
EDAT- 1995/01/01 00:00
MHDA- 1995/01/01 00:01
CRDT- 1995/01/01 00:00
PHST- 1995/01/01 00:00 [pubmed]
PHST- 1995/01/01 00:01 [medline]
PHST- 1995/01/01 00:00 [entrez]
AID - S027091399500019X [pii]
AID - 10.1016/0270-9139(95)90428-x [doi]
PST - ppublish
SO  - Hepatology. 1995 Jan;21(1):190-8. doi: 10.1016/0270-9139(95)90428-x.