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Updated: Sep 1, 2026
Kupffer Cell Isolation for Nanoparticle Toxicity Testing
Published on: August 18, 2015
Activation of Kupffer cells inhibits tumor growth in a murine model system
George G Chen1, Wan Y Lau, Paul B S Lai
1Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong. gchen@cuhk.edu.hk
Abstract:
Kupffer cells, a liver organ-specific macrophage, play an important role in preventing the development of malignant tumors. The mechanism responsible for their tumoricidal activities is not completely known. In our study, we established in vivo models involving a rat malignant cell line, rat Kupffer cells and tumor implantation in nude mice. A series of relevant in vitro experiments were also carried out to determine possible pathways. LPS-activated Kupffer cells produced significant amounts of NO, TNFalpha and IFNgamma. Malignant cells treated with either Kupffer cells or culture supernatant of the activated Kupffer cells had an increase in caspase-8 activity. Implanted tumors originated from malignant cells treated with either Kupffer cells or culture supernatant of the activated Kupffer cells grew much smaller than those from malignant cells without treatment or treated with control supernatants. The alteration of anti-apoptotic Bcl-2 was inversely associated with the change of pro-apoptotic caspase-8 and their levels in the tumor tissues matched the size of the tumors and treatments they received. It appeared that the above changes resulted in an increase in cellular DNA damage and apoptosis seen in malignant cells. Therefore, Kupffer cells execute their anti-tumor effect via increasing the production of NO, TNFalpha and IFNgamma and these cytotoxic molecules inhibit the growth of tumor by damaging cellular DNA and inducing apoptosis that was featured by downregulation of Bcl-2 but upregulation of caspase-8.
Insights
Kupffer cells, liver macrophages, prevent tumors by producing nitric oxide (NO), TNFalpha, and IFNgamma. These molecules induce malignant cell apoptosis and DNA damage, inhibiting tumor growth.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Kupffer cells are liver-resident macrophages crucial for immune surveillance.
- The precise mechanisms underlying Kupffer cell anti-tumor activity remain incompletely understood.
Purpose of the Study:
- To elucidate the mechanisms by which Kupffer cells exert their tumoricidal effects.
- To investigate the role of specific molecules and cellular pathways in Kupffer cell-mediated tumor suppression.
Main Methods:
- Established in vivo rat malignant cell line and Kupffer cell tumor implantation models in nude mice.
- Conducted in vitro experiments to analyze cellular responses and molecular pathways.
- Measured nitric oxide (NO), TNFalpha, and IFNgamma production by activated Kupffer cells.
- Assessed caspase-8 activity, Bcl-2 expression, DNA damage, and apoptosis in malignant cells.
Main Results:
- LPS-activated Kupffer cells produced significant levels of NO, TNFalpha, and IFNgamma.
- Malignant cells treated with Kupffer cells or their supernatant showed increased caspase-8 activity.
- Tumor growth was significantly inhibited in vivo when malignant cells were pre-treated with Kupffer cells or supernatant.
- Downregulation of anti-apoptotic Bcl-2 and upregulation of pro-apoptotic caspase-8 were observed, correlating with tumor size and treatment.
- Increased cellular DNA damage and apoptosis were evident in treated malignant cells.
Conclusions:
- Kupffer cells exert anti-tumor effects through the production of NO, TNFalpha, and IFNgamma.
- These cytotoxic molecules induce apoptosis and DNA damage in malignant cells, leading to tumor growth inhibition.
- The anti-tumor mechanism involves the downregulation of Bcl-2 and upregulation of caspase-8, promoting programmed cell death.
