Article

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

Institute of Immunology, University of Science and Technology of China, Hefei, Anhui 230027 China.
Liver international: official journal of the International Association for the Study of the Liver (impact factor: 3.82). 05/2006; 26(3):339-45. DOI:10.1111/j.1478-3231.2005.01221.x pp.339-45
Source: PubMed

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

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Keywords

accelerates liver regeneration
 
activation-induced cell death
 
apoptosis-related molecules
 
Con A-pretreated mice
 
Con A-primed NKT cells
 
Flow cytometric analysis
 
flow cytometry
 
Hepatic mononuclear cells
 
hepatic NKT cells
 
innate immune cells
 
intravenously 24 h
 
liver weight
 
NKT cells
 
nonhepatotoxic dose
 
nontoxic dose
 
phosphate-buffered saline-treated mice
 
proliferating cell nuclear antigen
 
remnant liver mass
 
subsequent liver regeneration
 
T cell stimulant
 

Wen Huang