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Involvement of the TNF and FasL produced by CD11b Kupffer cells/macrophages in CCl4-induced acute hepatic injury
- Source :
- PLoS ONE, Vol 9, Iss 3, p e92515 (2014), PLoS ONE
- Publication Year :
- 2014
- Publisher :
- Public Library of Science (PLoS), 2014.
-
Abstract
- We previously reported that F4/80(+) Kupffer cells are subclassified into CD68(+) Kupffer cells with phagocytic and ROS producing capacity, and CD11b(+) Kupffer cells with cytokine-producing capacity. Carbon tetrachloride (CCl4)-induced hepatic injury is a well-known chemical-induced hepatocyte injury. In the present study, we investigated the immunological role of Kupffer cells/macrophages in CCl4-induced hepatitis in mice. The immunohistochemical analysis of the liver and the flow cytometry of the liver mononuclear cells showed that clodronate liposome (c-lipo) treatment greatly decreased the spindle-shaped F4/80(+) or CD68(+) cells, while the oval-shaped F4/80+ CD11b(+) cells increased. Notably, severe hepatic injury induced by CCl4 was further aggravated by c-lipo-pretreatment. The population of CD11b(+) Kupffer cells/macrophages dramatically increased 24 hour (h) after CCl4 administration, especially in c-lipo-pretreated mice. The CD11b(+) Kupffer cells expressed intracellular TNF and surface Fas-ligand (FasL). Furthermore, anti-TNF Ab pretreatment (which decreased the FasL expression of CD11b(+) Kupffer cells), anti-FasL Ab pretreatment or gld/gld mice attenuated the liver injury induced by CCl4. CD1d-/- mouse and cell depletion experiments showed that NKT cells and NK cells were not involved in the hepatic injury. The adoptive transfer and cytotoxic assay against primary cultured hepatocytes confirmed the role of CD11b(+) Kupffer cells in CCl4-induced hepatitis. Interestingly, the serum MCP-1 level rapidly increased and peaked at six h after c-lipo pretreatment, suggesting that the MCP-1 produced by c-lipo-phagocytized CD68(+) Kupffer cells may recruit CD11b(+) macrophages from the periphery and bone marrow. The CD11b(+) Kupffer cells producing TNF and FasL thus play a pivotal role in CCl4-induced acute hepatic injury.
- Subjects :
- Male
Adoptive cell transfer
Physiology
lcsh:Medicine
Pathology and Laboratory Medicine
Immunoenzyme Techniques
Mice
Animal Cells
Immune Physiology
Medicine and Health Sciences
Cytotoxic T cell
lcsh:Science
Carbon Tetrachloride
Cells, Cultured
Mice, Knockout
Liver injury
Mice, Inbred BALB C
Multidisciplinary
Chemistry
CD68
Liver Diseases
Animal Models
Flow Cytometry
Natural killer T cell
Killer Cells, Natural
medicine.anatomical_structure
Hepatocyte
Tumor necrosis factor alpha
Cellular Types
Chemical and Drug Induced Liver Injury
Immunohistochemical Analysis
Molecular Pathology
Research Article
Fas Ligand Protein
Kupffer Cells
Immune Cells
Mouse Models
Gastroenterology and Hepatology
Research and Analysis Methods
digestive system
Model Organisms
Diagnostic Medicine
medicine
Animals
Immunohistochemistry Techniques
Tumor Necrosis Factor-alpha
Macrophages
lcsh:R
Biology and Life Sciences
Cell Biology
Liver Failure, Acute
medicine.disease
Molecular biology
Histochemistry and Cytochemistry Techniques
Mice, Inbred C57BL
Immunology
Hepatocytes
lcsh:Q
Bone marrow
Antigens, CD1d
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 9
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....fc692d6bdc364df433ca1710bc54cd2c