PMID- 30614543 OWN - NLM STAT- MEDLINE DCOM- 20200519 LR - 20200519 IS - 1537-2995 (Electronic) IS - 0041-1132 (Linking) VI - 59 IP - 4 DP - 2019 Apr TI - Stored red blood cells enhance in vivo migration of dendritic cells by promoting reactive oxygen species-induced cytoskeletal rearrangement. PG - 1312-1323 LID - 10.1111/trf.15123 [doi] AB - BACKGROUND: A complex array of physicochemical changes occurs in red blood cells (RBCs) during storage, leading to enhanced posttransfusion clearance. Dendritic cells (DCs) play crucial roles in the engulfment of aged RBCs; however, it is unclear how stored RBCs (sRBCs) modulate their responses to inflammatory stimuli and DC migration ability. STUDY DESIGN AND METHODS: In this study, we examined whether sRBCs affect the migration ability of DCs and elucidated the detailed mechanisms mediating this process. Murine RBCs were incubated with marrow DCs after removing the storage supernatant. The effects of sRBCs on cytokine secretion from DCs, surface marker expression, and homing ability were examined. RESULTS: More sRBCs were internalized by DCs than fresh RBCs (fRBCs), and RBC accumulation significantly promoted the expression of allostimulatory molecules and the secretion of Th1-type cytokines in the presence of lipopolysaccharide (LPS). In particular, the lymphoid-tissue homing ability of transfused DCs treated with sRBCs (sRBC-DCs) was also significantly greater than that of fRBCs. Up regulation of CCR7 and improved organization of the cytoskeleton were observed in sRBC-DCs, and blocking Rho/Rho-associated protein kinase (ROCK), PI3K/Akt, and NF-kappaB pathways greatly hindered cytoskeletal rearrangement. Moreover, high levels of reactive oxygen species (ROS) were detected in sRBC-DCs, and treatment with N-acetylcysteine simultaneously decreased the lymph node-homing ability of DCs and phosphorylation of RhoA, ROCK1, and cortactin. CONCLUSIONS: sRBCs initiated differential immune responses compared to fRBCs, and the presence of LPS augmented this phenomenon. Up regulation of CCR7 and ROS production promotes cytoskeletal reorganization and contributes to the increased homing of sRBCs-DCs. CI - (c) 2019 AABB. FAU - Zhao, Man AU - Zhao M AD - Beijing Key Laboratory of Blood Safety and Security, Institute of Health Service and Transfusion Medicine, Beijing, P.R. China. AD - Department of Blood Transfusion, Chinese PLA General Hospital, Beijing, China. FAU - Zhou, Qianqian AU - Zhou Q AD - Beijing Key Laboratory of Blood Safety and Security, Institute of Health Service and Transfusion Medicine, Beijing, P.R. China. FAU - He, Chulin AU - He C AD - Beijing Key Laboratory of Blood Safety and Security, Institute of Health Service and Transfusion Medicine, Beijing, P.R. China. FAU - Zhang, Yulong AU - Zhang Y AD - Beijing Key Laboratory of Blood Safety and Security, Institute of Health Service and Transfusion Medicine, Beijing, P.R. China. FAU - Wang, Zhengjun AU - Wang Z AD - Beijing Key Laboratory of Blood Safety and Security, Institute of Health Service and Transfusion Medicine, Beijing, P.R. China. FAU - Cai, Ruiying AU - Cai R AD - Beijing Key Laboratory of Blood Safety and Security, Institute of Health Service and Transfusion Medicine, Beijing, P.R. China. FAU - Ma, Cong AU - Ma C AD - Beijing Key Laboratory of Blood Safety and Security, Institute of Health Service and Transfusion Medicine, Beijing, P.R. China. FAU - Li, Yuan AU - Li Y AD - Beijing Key Laboratory of Blood Safety and Security, Institute of Health Service and Transfusion Medicine, Beijing, P.R. China. FAU - Wang, Xiaohui AU - Wang X AD - Beijing Key Laboratory of Blood Safety and Security, Institute of Health Service and Transfusion Medicine, Beijing, P.R. China. FAU - Zhan, Linsheng AU - Zhan L AD - Beijing Key Laboratory of Blood Safety and Security, Institute of Health Service and Transfusion Medicine, Beijing, P.R. China. AD - Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190107 PL - United States TA - Transfusion JT - Transfusion JID - 0417360 RN - 0 (Reactive Oxygen Species) SB - IM MH - Animals MH - *Blood Preservation MH - Cell Movement/*immunology MH - Cytoskeleton/*immunology MH - Dendritic Cells/cytology/*immunology MH - Erythrocytes/cytology/*immunology MH - Gene Expression Regulation/immunology MH - Male MH - Mice MH - Reactive Oxygen Species/*immunology MH - Signal Transduction/immunology EDAT- 2019/01/08 06:00 MHDA- 2020/05/20 06:00 CRDT- 2019/01/08 06:00 PHST- 2018/04/12 00:00 [received] PHST- 2018/10/27 00:00 [revised] PHST- 2018/10/28 00:00 [accepted] PHST- 2019/01/08 06:00 [pubmed] PHST- 2020/05/20 06:00 [medline] PHST- 2019/01/08 06:00 [entrez] AID - 10.1111/trf.15123 [doi] PST - ppublish SO - Transfusion. 2019 Apr;59(4):1312-1323. doi: 10.1111/trf.15123. Epub 2019 Jan 7.