NLRP3 Inflammasome Activation Regulates Aged RBC Clearance

被引:9
|
作者
Li Qin [1 ]
Zhao Fengyong [1 ,2 ]
Zhang Jiamin [1 ]
Yang Qixiu [1 ]
Lu Geming [3 ]
Xia Rongwei [4 ]
Zhu Ziyan [1 ]
机构
[1] Shanghai Blood Ctr, Blood Grp Reference Lab, Hongqiao Rd 1191, Shanghai 200051, Peoples R China
[2] East China Normal Univ, Sch Life Sci, Shanghai, Peoples R China
[3] Icahn Sch Med Mt Sinai, Diabet Obes & Metab Inst, Mindich Child Hlth & Dev Inst, Div Endocrinol Diabet & Bone Dis, New York, NY USA
[4] Yunnan Qujing Cent Blood Stn, Qujing, Yunnan, Peoples R China
关键词
NLRP3; inflammasome; aged erythrocytes; cytokines; THP-1; RED-BLOOD-CELLS; IN-VIVO; CD47; TRANSFUSION; EXPRESSION; STORAGE; ERYTHROCYTES; METAANALYSIS; MACROPHAGES; VESICLES;
D O I
10.1007/s10753-018-0784-9
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The NLR family pyrin domain-containing protein 3 (NLRP3) inflammasome is triggered by various stimuli. Whether the NLRP3 inflammasome is activated during the monocyte clearing of aged or damaged erythrocytes is unknown. This work aimed to determine whether the NLRP3 inflammasome is activated during the THP-1 cell engulfing of aged erythrocytes. In the study, THP-1 cells were treated with PMA and then coincubated with untreated red blood cells (RBCs), 42 A degrees C-treated RBCs, immunoglobulin G (IgG) anti-D-sensitized RBCs, Rhnull/Rhmod RBC sample, hemoglobin, and RBC ghost. The activation of the NLRP3 inflammasome and production of some proinflammatory cytokines were determined using immunoblotting, cytometric bead array, and digital PCR. An NLRP3 inflammasome inhibitor was also used to evaluate the alteration of the NLRP3 activation and RBC clearance rate. The untreated RBCs, 42 A degrees C-incubated RBCs, IgG-opsonized RBCs, Rhnull/Rhmod RBCs, RBC ghosts, and hemoglobin induced the THP-1-cell-mediated activation of the NLRP3 inflammasome and the production of inflammatory cytokines. The RBC clearance rate exhibited a positive correlation with the expression of proinflammatory cytokines. The NLRP3 inflammasome inhibitor reduced the NLRP3 activation and RBC phagocytosis rate. The NLRP3 inflammasome was activated during the clearance of the aged erythrocytes through unopsonized and opsonized pathways. However, the mechanism of such phenomenon needs to be further elucidated. Such mechanism may provide new insight into the assessment of the safety of transfusing long-storage RBC based on cytokine levels.
引用
收藏
页码:1361 / 1371
页数:11
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