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Cited by 86Transplantation: Methods and OutcomesOrgan Transplantation Techniques and OutcomesLiver physiology and pathology

Role of Kupffer cells in the induction of tolerance of orthotopic liver transplantation in rats

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Chen, Yong, Liu, Zuojin, Liang, Shaoyong, Luan, Xiaofeng, Long, Feiwu, Chen, Jie, Peng, Yong, Yan, Lünan +1 more·2008·Liver Transplantation
DOI 10.1002/lt.21450
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Abstract

Because the role of Kupffer cells (KCs) in liver transplantation (LT) tolerance is not well understood, we investigated their role in liver allograft acceptance in rats. Male Sprague-Dawley rats were randomly assigned to either an LT group or a transplantation group pretreated with GdCl(3) (Gd group). The rats were postoperatively sacrificed at indicated times for histology and assessment of KC function, nuclear factor kappa B (NF-kappaB) activity, and cytokine production. KCs and T cells (TCs) were isolated from allografts to assess Fas/Fas ligand (FasL) expression. Cytotoxicity of KCs against TCs was monitored by coculturing of (3)H-thymidine TCs with KCs at various effector-to-target ratios. The results were as follows. First, grafts were spontaneously accepted in the LT group with evident apoptosis of TCs; however, inhibition of KCs by pretreatment with GdCl(3) decreased TC apoptosis and shortened the survival of allografts. Second, KCs in the LT group had increased levels of FasL messenger RNA and protein with respect to that in the Gd group. Third, by in vitro cocultivation assays, KCs induced TC apoptosis though elevated expression of FasL, and this process could be blocked by anti-FasL antibody. Fourth, there was a positive correlation between activation of NF-kappaB and FasL expression in KCs and interleukin-4 production in the LT group, and the activation of NF-kappaB was inhibited by pretreatment with GdCl(3). In conclusion, KC-induced depletion of TCs via the Fas/FasL pathway might play a critical role in LT tolerance. However, the tolerance is abrogated by suppression of FasL and IL-4 expression via inhibition of NF-kappaB activity by GdCl(3).

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  • An essential histological feature of MASH is diffuse infiltration of the liver by mononuclear cells, often organising into focal aggregates resembling tertiary lymphoid structures.

    “An essential histological feature of MASH is diffuse infiltration of the liver by mononuclear cells, often organising into focal aggregates resembling tertiary lymphoid structures (27).”

    From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [27]

    The Pathological Alterations section describes neutrophil and T-cell infiltration during acute rejection of rat liver allografts, not the histology of MASH. Searches for MASH-related infiltration and tertiary lymphoid-like focal aggregates found no passage addressing the claimed feature; page numbers were not available in our copy. (LLM, conf=0.76)

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Cited by

Sorted by citations

Authors
Chen, Y., Liu, Z., Liang, S., Luan, X., Long, F., Chen, J., Peng, Y., Yan, L., & Gong, J.
Affiliations
Sichuan University (CN)
Corresponding author
  • Yan, Lünan
  • Gong, Jianping
ORCID
Venue
Liver Transplantation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2008
Volume
14
Issue
6
Pages
823-836
ISSN
  • 1527-6465 (ISSN-L)
  • 1527-6473
DOI
10.1002/lt.21450
OpenAlex
W2023036885
Cited by
86
References
0
Citations by year
2026: 2 · 2025: 6 · 2024: 5 · 2023: 7 · 2022: 2 · 2021: 2 · 2020: 9 · 2019: 3 · 2018: 6 · 2017: 6 · 2016: 6 · 2015: 4 · 2014: 8 · 2013: 1 · 2012: 5
FWCI
4.92
Type
journal article
Language
en
Open access
Licence
doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 2800 d)
Locations
  • Liver Transplantation (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (30471696)
  • Natural Science Foundation of Chongqing
Topics
  • Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
  • Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords
Kupffer cells, orthotopic liver transplantation, graft tolerance, allograft acceptance, Fas/Fas ligand pathway, T cell apoptosis, NF-κB activation, IL-4, gadolinium chloride, allograft survival, cytokine production
MeSH terms
Animals, Immune Tolerance, Kupffer Cells, Male, Models, Biological, Phagocytosis, RNA, Messenger, Interleukin-4, Liver Transplantation, NF-kappa B, Rats, Sprague-Dawley, Apoptosis, fas Receptor, Rats, Fas Ligand Protein

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