Selective elimination of hepatic natural killer T cells with Concanavalin A improves liver regeneration in mice

Authors

  • Wen Huang,

    1. Institute of Immunology, University of Science and Technology of China, Hefei, Anhui 230027 China,
    Search for more papers by this author
    • *These authors equally contribute to this work.

  • Zhongjun Dong,

    1. Institute of Immunology, University of Science and Technology of China, Hefei, Anhui 230027 China,
    Search for more papers by this author
    • *These authors equally contribute to this work.

  • Haiming Wei,

    1. Institute of Immunology, University of Science and Technology of China, Hefei, Anhui 230027 China,
    Search for more papers by this author
  • Chen Ding,

    1. Institute of Immunology, University of Science and Technology of China, Hefei, Anhui 230027 China,
    Search for more papers by this author
  • Rui Sun,

    1. Institute of Immunology, University of Science and Technology of China, Hefei, Anhui 230027 China,
    2. School of Pharmacy, Shandong University, Wenhua Western Road, Jinan, Shandong 250012, China
    Search for more papers by this author
  • Zhigang Tian

    1. Institute of Immunology, University of Science and Technology of China, Hefei, Anhui 230027 China,
    2. School of Pharmacy, Shandong University, Wenhua Western Road, Jinan, Shandong 250012, China
    Search for more papers by this author

Dr. Zhigang Tian, School of Life Sciences, University of Science and Technology of China 443 Huangshan Road, Hefei, Anhui 230027, China.
Tel: +86-551-360-7379
Fax: +86-551-360-6783
e-mail: tzg@ustc.edu.cn

Abstract

Abstract: Background: Although concanavalin A (Con A) as a T cell stimulant can cause natural killer T (NKT) cell-mediated liver injury in mice and a nonhepatotoxic dose of Con A can trigger innate immune cells including NKT cells to prevent tumor metastasis in the liver, little is known about the role of Con A-primed NKT cells in liver repair. In this study, we aimed to investigate the effect of pretreatment with a nontoxic dose of Con A on subsequent liver regeneration in mice.

Methods: A nontoxic dose of Con A was injected intravenously 24 h before partial hepatectomy (PHx), which was used as a model of liver regeneration. Ratios of remnant liver mass to body weight, bromodeoxyuridine (BrdU) incorporation and proliferating cell nuclear antigen (PCNA) labeling were used to assess liver regeneration.

Results: Hepatic mononuclear cells were isolated and analyzed by flow cytometry. After PHx, the ratios of liver weight to body weight, PCNA-positive hepatocytes and BrdU-positive hepatocytes in Con A-pretreated mice were significantly higher than that of phosphate-buffered saline-treated mice, indicating that Con A pretreatment can accelerate liver regeneration. Flow cytometric analysis showed that NKT cells were significantly activated and selectively eliminated after the Con A administration. Moreover, NKT cells expressed more apoptosis-related molecules, Fas and Annexin V.

Conclusions: Taken together, Con A accelerates liver regeneration in mice by eliminating hepatic NKT cells via activation-induced cell death.

Ancillary