Abstract
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. This study aimed to elucidate the correlation among erythrocyte transfusion, macrophage pyroptosis and inflammation in the progression of sepsis. 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. 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. Erythrocyte transfusion may function as a therapeutic tool against sepsis by regulating pyroptosis, inflammation and cytotoxicity.
Highlights
Sepsis is one of most common causes of death in the intensive care unit (ICU) due to infection and inflammation
Erythrocyte transfusion may function as a therapeutic tool against sepsis by regulating pyroptosis, inflammation and cytotoxicity
Flow cytometry results showed that the expression of Duffy antigen receptor for chemokines (DARC) in septic rats injected with erythrocytes (Fig. 2A) was upregulated compared to the control animals (Fig. 2B)
Summary
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, playing an important role in inflammation. The Duffy antigen receptor for chemokines (DARC) is an atypical receptor that regulates pro-inflammatory cytokines.[1] It is expressed in multiple tissues, including kidney and brain.[2,3] It has been reported that DARC plays a role in erythrocyte function. DARC found on the surface of erythrocytes facilitates chemokine reception.[4] Staphylococcus aureus has been shown to target DARC to lyse erythrocytes within the mammalian host.[5] The DARC is engaged in Plasmodium spp.-induced red blood cell invasion.[6] DARC regulates inflammatory responses in adipose tissues,[7] asthma[1] and fractures.[8] DARC may act as a critical regulator in inflammation-related pathological processes
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