Da-Long Zhang1, Shun-Wen Zhang2, Qing Hong Cheng1, Fang Wu3, Jiang-Dong Wu3, Jie Zhang1, Jiang-Tao Dong1, Hui-Yun Zhu3, Shuai Zhang3, Qing-Qing Wu1, Wan-Jiang Zhang1,3. 1. The First Affiliated Hospital, School of Medicine, Shihezi UniversityShihezi 832002, Xinjiang, China. 2. School of Basic Medical Sciences, Nanjing Medical UniversityNanjing 211166, Jiangsu Province, China. 3. The Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Department of Pathophysiology, School of Medicine, Shihezi University, Collaborative Innovation Center of High Incidence of Zoonoses Communicable Disease Prevention in the Western RegionShihezi 832002, Xinjiang, China.
Abstract
OBJECTIVE: To investigate the effect of peritoneal macrophage autophagy on immune function in sepsis mice. METHODS: Seventy-two male BALB/C mice were intraperitoneally injected with LPS to induce sepsis. The mice were randomly divided into six groups: LPS+2 h, LPS+6 h, LPS+12 h, LPS+24 h and LPS+36 h. LPS with a dose of 10 mg/kg was intraperitoneally injected into the abdominal cavity of the sepsis mice, and the control group was injected with the same dose of saline. ELISA was used to detect the concentrations of inflammatory factors IL-2, IL-10 and TNF-α in the peripheral blood, and the CD4+T/CD8+T ratio in the peripheral blood was detected by flow cytometry. The expression levels of LC3II and Beclin-1/beta-action in the mouse macrophages were measured using Western blot to determine the level of autophagy. RESULTS: The expression levels of LC3II and Beclin-1 were significantly higher in the peritoneal macrophages of the mice from the LPS+2 h group than in those of the mice from the normal group (P<0.05). Meanwhile, these levels continuously declined in the LPS+6 h, LPS+12 h, LPS+24 h and LPS+36 h groups (P<0.05). The peripheral blood CD4+T/CD8+T cell ratio was significantly higher in the LPS+2 h and LPS+6 h groups than in the normal group (P<0.05). The ratio peaked at 6 h and then continuously declined (P<0.05). Furthermore, the concentrations of IL-2 and Tnf-α were significantly higher in the peripheral blood serum of the LPS+2 h, LPS+6 h and LPS+12 h groups than in those of the normal group (P<0.05). The peak was observed at 12 h followed by a continuous decline in the LPS+24 h and 3 LPS+6 h groups (P<0.05). The peripheral serum IL-10 concentration was significantly higher in the LPS+2 h, LPS+6 h, LPS+12 h, LPS+24 h and LPS+36 h groups than in the normal group (P<0.05). In the LPS+6 h, LPS+12 h, LPS+24 h and LPS+36 h groups, the peritoneal macrophages LC3II, Beclin-1 and peripheral serum CD+4T/CD+8T ratio correlation index R2=0.716 (P=0.043), R2=0.954 (P=0.023). CONCLUSION: Autophagy in peritoneal macrophages plays an important role in the immune function of sepsis mice. In addition, the autophagy of peritoneal macrophages and the immune function of sepsis mice are strongly correlated. Furthermore, macrophage autophagy plays an important role in the immune function changes in sepsis mice, and the underlying mechanism may be involved in inflammation and macrophage antigen presentation by regulating the secretion of inflammatory cytokines and lymphocyte apoptosis antagonism.
OBJECTIVE: To investigate the effect of peritoneal macrophage autophagy on immune function in sepsismice. METHODS: Seventy-two male BALB/C mice were intraperitoneally injected with LPS to induce sepsis. The mice were randomly divided into six groups: LPS+2 h, LPS+6 h, LPS+12 h, LPS+24 h and LPS+36 h. LPS with a dose of 10 mg/kg was intraperitoneally injected into the abdominal cavity of the sepsismice, and the control group was injected with the same dose of saline. ELISA was used to detect the concentrations of inflammatory factors IL-2, IL-10 and TNF-α in the peripheral blood, and the CD4+T/CD8+T ratio in the peripheral blood was detected by flow cytometry. The expression levels of LC3II and Beclin-1/beta-action in the mouse macrophages were measured using Western blot to determine the level of autophagy. RESULTS: The expression levels of LC3II and Beclin-1 were significantly higher in the peritoneal macrophages of the mice from the LPS+2 h group than in those of the mice from the normal group (P<0.05). Meanwhile, these levels continuously declined in the LPS+6 h, LPS+12 h, LPS+24 h and LPS+36 h groups (P<0.05). The peripheral blood CD4+T/CD8+T cell ratio was significantly higher in the LPS+2 h and LPS+6 h groups than in the normal group (P<0.05). The ratio peaked at 6 h and then continuously declined (P<0.05). Furthermore, the concentrations of IL-2 and Tnf-α were significantly higher in the peripheral blood serum of the LPS+2 h, LPS+6 h and LPS+12 h groups than in those of the normal group (P<0.05). The peak was observed at 12 h followed by a continuous decline in the LPS+24 h and 3 LPS+6 h groups (P<0.05). The peripheral serum IL-10 concentration was significantly higher in the LPS+2 h, LPS+6 h, LPS+12 h, LPS+24 h and LPS+36 h groups than in the normal group (P<0.05). In the LPS+6 h, LPS+12 h, LPS+24 h and LPS+36 h groups, the peritoneal macrophages LC3II, Beclin-1 and peripheral serum CD+4T/CD+8T ratio correlation index R2=0.716 (P=0.043), R2=0.954 (P=0.023). CONCLUSION: Autophagy in peritoneal macrophages plays an important role in the immune function of sepsismice. In addition, the autophagy of peritoneal macrophages and the immune function of sepsismice are strongly correlated. Furthermore, macrophage autophagy plays an important role in the immune function changes in sepsismice, and the underlying mechanism may be involved in inflammation and macrophage antigen presentation by regulating the secretion of inflammatory cytokines and lymphocyte apoptosis antagonism.
Entities:
Keywords:
Macrophage; autophagy immune function change; sepsis disease
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