Brief Article
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World J Gastroenterol. Oct 7, 2013; 19(37): 6258-6264
Published online Oct 7, 2013. doi: 10.3748/wjg.v19.i37.6258
Research on stress-induced apoptosis of natural killer cells and the alteration of their killing activity in mouse liver
Zhen Ma, Yang Liu, Xin Zhou, Hai-Long Yu, Ming-Qi Li, Chikako Tomiyama-Miyaji, Toru Abo, Xue-Feng Bai
Zhen Ma, Xin Zhou, Hai-Long Yu, Ming-Qi Li, Xue-Feng Bai, Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin 150040, Heilongjiang Province, China
Yang Liu, Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China
Chikako Tomiyama-Miyaji, Toru Abo, Department of Immunology, Niigata University School of Medicine, Niigata 951-8510, Japan
Author contributions: Ma Z and Liu Y carried out the experimental work; Ma Z and Liu Y contributed equally to this study and should be regarded as first joint authors; Ma Z, Liu Y, Zhou X and Li MQ participated in the data collection; Zhou X contributed to the analysis of data and preparation of the manuscript; Yu HL carried out partial experimental work and manuscript preparation; Li MQ carried out the data interpretation; Tomiyama-Miyaji C, Abo T and Bai XF participated in the study design; Bai XF carried out the coordination of experimental work, the analysis and interpretation of data and drafted the manuscript.
Supported by The National Natural Science Foundation of China, No.30671899, No.30540012
Correspondence to: Xue-Feng Bai, PhD, Professor, Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Haping Street 150, Harbin 150040, Heilongjiang Province, China. drbaixuefeng@163.com
Telephone: +86-451-86298096 Fax: +86-451-86298756
Received: May 7, 2013
Revised: July 21, 2013
Accepted: August 8, 2013
Published online: October 7, 2013
Abstract

AIM: To investigate the stress-induced apoptosis of natural killer (NK) cells and the changes in their killing activity in mouse livers.

METHODS: A restraint stress model was established in mice. Flow cytometry was employed to measure the percentage of NK cells and the changes in their absolute number in mouse liver. The cytotoxicity of hepatic and splenic NK cells was assessed against YAC-1 target cells via a 4 h 51Cr-release assay.

RESULTS: The restraint stress stimulation induced the apoptosis of NK cells in the liver and the spleen, which decreased the cell number. The number and percentage of NK cells in the spleen decreased. However, the number of NK cells in the liver decreased, whereas the percentage of NK cells was significantly increased. The apoptosis of NK cells increased gradually with prolonged stress time, and the macrophage-1 (Mac-1)+ NK cells were more susceptible to apoptosis than Mac-1- NK cells. Large numbers of Mac-1- NK cells in the liver, which are more resistant to stress-induced apoptosis, were observed than the Mac-1- NK cells in the spleen. The stress stimulation diminished the killing activity of NK cells in the spleen was significantly decreased, but the retention of numerous Mac-1- NK cells in the liver maintained the killing ability.

CONCLUSION: Significant stress-induced apoptosis was observed among Mac-1+ NK cells, but not Mac-1- NK cells in the mouse liver. Stress stimulation markedly decreased the killing activity of NK cells in the spleen but remained unchanged in the liver.

Keywords: Restraint stress, Natural killer cells, Cell apoptosis, Killing activity

Core tip: Hepatic natural killer (NK) cells are classified into macrophage-1 (Mac-1)+ and Mac-1- cells, and the different functional characteristics of Mac-1+ or Mac-1- NK cells in response to stress stimulation are confirmed. This study further proves the heterogeneity of NK cell function, and the results provide a reference for preventing the immune system damage caused by stress.