The effect of erythrocyte transfusion on macrophage pyroptosis and inflammation in a sepsis model.
The effect of erythrocyte transfusion on macrophage pyroptosis and inflammation in a sepsis model.
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DOI：
10.17219/acem/133490
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发表时间：
2021-05
期刊：
影响因子：
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通讯作者：
Zhen-Zhou Li;Huan Wang;Jin-huo Wang;Xiao-Fang Zhou;Jia-Ming Xu;Yong Cheng;Xun Zhou;Jianrong Guo-Ji
中科院分区：
文献类型：
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作者：
Zhen-Zhou Li;Huan Wang;Jin-huo Wang;Xiao-Fang Zhou;Jia-Ming Xu;Yong Cheng;Xun Zhou;Jianrong Guo-Ji
背景脓毒症是重症监护病房（ICU）中因感染和炎症导致的最常见死亡原因之一。Duffy抗原趋化因子受体（DARC）调节促炎细胞因子，从而在炎症中发挥重要作用。本研究旨在阐明红细胞输注、巨噬细胞凋亡和炎症在脓毒症进展中的相关性。材料与方法丙氨酸氨基转移酶（ALT/GPT）活性测定试剂盒（南京建成生物）按试剂盒说明书进行测定。根据试剂盒手册，使用内皮素-1（ET-1）测定试剂盒（Jiancheng Bio），通过酶联免疫吸附测定（ELISA）测定ET-1浓度。采用流式细胞仪Annexin V染色法检测细胞凋亡。使用离心收集细胞并重悬于结合缓冲液中。采用酶联免疫吸附法（ELISA）检测各组大鼠血浆白细胞介素（IL）-1β、IL-18、IL-33、MIP-2、CXCL 8、活性氧（ROS）和LTB 4水平。结果脓毒症大鼠肝功能损害，ET-1水平降低。在脓毒症模型中，红细胞输注上调DARC表达。红细胞输注还影响巨噬细胞中的焦亡，减少炎性细胞因子如IL-1β、IL-18和IL-33的产生，并减轻脓毒症模型中的细胞毒性。结论红细胞输注可通过调节脓毒症的细胞毒作用、炎症反应和细胞毒作用而发挥治疗脓毒症的作用。
BACKGROUND Sepsis is one of most common causes of death in the intensive care unit (ICU) due to infection and inflammation. The Duffy antigen receptor for chemokines (DARC) regulates pro-inflammatory cytokines, thus playing an important role in inflammation. OBJECTIVES This study aimed to elucidate the correlation among erythrocyte transfusion, macrophage pyroptosis and inflammation in the progression of sepsis. MATERIAL AND METHODS Alanine aminotransferase (ALT/GPT) activity was measured with the ALT/GPT activity measurement kit (Jiancheng Bio, Nanjing, China) according to the kit manual. The ET-1 concentration was measured with enzyme-linked immunosorbent assay (ELISA) using the endothelin-1 (ET-1) measurement kit (Jiancheng Bio) according to the kit manual. Apoptosis was evaluated using flow cytometry-based Annexin V staining assay. The cells were collected using centrifugation and resuspended in binding buffer. Ultrastructural analysis of pyroptotic body, the levels of interleukin (IL)-1β, IL-18, IL-33, MIP-2, CXCL8, reactive oxygen species (ROS), and LTB4 were measured with ELISA. RESULTS Our results showed that septic rats had impaired hepatic function and ET-1 levels. Erythrocyte transfusion upregulated DARC expression in the sepsis model. Erythrocyte transfusion also affected pyroptosis in macrophages, reduced the production of inflammatory cytokines, such as IL-1β, IL-18 and IL-33, and alleviated cytotoxicity in the sepsis model. CONCLUSIONS Erythrocyte transfusion may function as a therapeutic tool against sepsis by regulating pyroptosis, inflammation and cytotoxicity.