文献类型：期刊文献

英文题名：Red blood cells undergo lytic programmed cell death involving NLRP3

作者：Chen, Yaozhen[1];Chen, Shouwen[2];Liu, Zhixin[1];Wang, Yafen[1];An, Ning;Chen, Yutong[1];Peng, Yihao;Liu, Zheng[3];Liu, Qin[2];Hu, Xingbin[1]

机构：[1]Fourth Mil Med Univ, Xijing Hosp, Dept Transfus Med, Xian 710032, Shaanxi, Peoples R China;[2]East China Univ Sci & Technol, Shanghai Frontiers Sci Ctr Optogenet Tech Cell Met, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[3]Chinese Univ Hong Kong, Kobilka Inst Innovat Drug Discovery, Sch Med, Shenzhen 518115, Guangdong, Peoples R China

年份：2025

卷号：188

期号：11

起止页码：3013

外文期刊名：CELL

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001504744800013)】；

基金：The authors would like to thank Dr. C. Zhang, Dr. B.C. Che, and Y.G. Tian for the video analysis; Dr. D.D. Yin for clinical consulting; Prof. F. Shao and H.B. Zhang for providing knockout mice; and D.L. Si and Y.Q. Li from the analysis & testing laboratory for life sciences and medicine of the Air Force Medical Uni-versity for morphological observation. This research was supported by the Na-tional Key Research and Development Plan of China (no. 2022YFC3400103 to Q.L. and X.H.) , the National Natural Science Foundation of China (no. 32025038 to Q.L.; no. 82370230 to X.H.) , and the ECUST-OPM Open Fund (no. 20220701 to Q.L.) .

语种：英文

摘要：The canonical complement-mediated lysis of mature red blood cells (RBCs) leads to severe pathogenesis. However, inhibition strategies targeting complement are not always as efficient as expected, indicating that unknown mechanisms are awaiting elucidation. In this study, we investigate the intracellular events in mature RBCs following complement activation. The collected evidence demonstrates that complement-induced hemolysis is a caspase-8-dependent programmed RBC death. Furthermore, short NLRP3 (min-iNLRP3) fragments in RBCs are identified to engage in the assembly of NLRP3-apoptosis-associated speck-like protein containing a CARD (ASC)-caspase-8 complex. Activated caspase-8 directly induces the proteolysis of b-spectrin, thereby disrupting the skeletal network of the RBC membrane, a process we refer to as spectosis. Spectosis signaling is also activated in autoimmune hemolytic anemia or paroxysmal nocturnal hemoglobinuria, and the inhibition of spectosis significantly reduced complement-induced hemolysis. These findings reveal a programmed death cascade in mature RBCs, which may have important implications for the treatment of hemolytic disorders.