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Published on: March 24, 2015
Possible Involvement of Liver Resident Macrophages (Kupffer Cells) in the Pathogenesis of Both Intrahepatic and
Yuki Kakinuma1, Takuya Kimura1, Yoshifumi Watanabe1
1Department of Pharmaceutical Sciences, Musashino University, Tokyo 202-0023, Japan.
Abstract:
Liver resident macrophages designated Kupffer cells (KCs) form the largest subpopulation of tissue macrophages. KCs are involved in the pathogenesis of liver inflammation. However, the role of KCs in the systemic inflammation is still elusive. In this study, we examined whether KCs are involved in not only intrahepatic inflammation but also extrahepatic systemic inflammation. Administration of clodronate liposomes resulted in the KC deletion and in the suppression of liver injury in T cell-mediated hepatitis by ConA as a local acute inflammation model, while the treatment did not influence dextran sulfate sodium- (DSS-) induced colitis featured by weight loss, intestinal shrink, and pathological observation as an ectopic local acute inflammation model. In contrast, KC deletion inhibited collagen-induced arthritis as a model of extrahepatic, systemic chronical inflammation. KC deleted mice showed weaker arthritic scores, less joint swelling, and more joint space compared to arthritis-induced control mice. These results strongly suggest that KCs are involved in not only intrahepatic inflammatory response but also systemic (especially) chronic inflammation.
Insights
Kupffer cells (KCs) drive liver inflammation and also contribute to systemic chronic inflammation, such as in arthritis. Deleting KCs reduced liver injury and inhibited arthritis development.
Area of Science:
- Immunology
- Hepatology
- Rheumatology
Background:
- Kupffer cells (KCs) are liver-resident macrophages crucial for hepatic inflammation.
- Their precise role in systemic inflammation, particularly chronic conditions, remains unclear.
Purpose of the Study:
- To investigate the involvement of KCs in both intrahepatic and extrahepatic inflammation.
- To determine if KCs contribute to systemic chronic inflammatory diseases.
Main Methods:
- KC depletion using clodronate liposomes in mouse models.
- Assessment of ConA-induced T cell-mediated hepatitis (local acute inflammation).
- Evaluation of DSS-induced colitis (ectopic local acute inflammation) and collagen-induced arthritis (systemic chronic inflammation).
Main Results:
- KC depletion suppressed ConA-induced hepatitis but did not affect DSS-induced colitis.
- KC deletion significantly inhibited collagen-induced arthritis, reducing disease severity.
- Mice lacking KCs exhibited milder arthritis symptoms and joint damage.
Conclusions:
- Kupffer cells play a significant role in intrahepatic inflammation.
- KCs are critically involved in the pathogenesis of systemic chronic inflammation, notably arthritis.
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