Selective elimination of hepatic natural killer T cells with concanavalin A improves liver regeneration in mice.
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.
Institute of Immunology, University of Science and Technology of China, Hefei, Anhui 230027 China.
Wen
W
Huang
Zhongjun
Z
Dong
Haiming
H
Wei
Chen
C
Ding
Rui
R
Sun
Zhigang
Z
Tian
D000410:Alanine Transaminase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D003208:Concanavalin A / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D022781:Hepatocytes / Q000378:metabolism; D007150:Immunohistochemistry; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000503:physiopathology; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008934:Mitogens / Q000008:administration & dosage / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D018809:Proliferating Cell Nuclear Antigen; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D000964:Antimetabolites, Antineoplastic; D008934:Mitogens; D018809:Proliferating Cell Nuclear Antigen; D003208:Concanavalin A; D000410:Alanine Transaminase; D001973:Bromodeoxyuridine