Cholesterol accumulation in macrophages drives NETosis in atherosclerotic plaques via IL-1β secretion.
Cholesterol accumulation in macrophages drives NETosis in atherosclerotic plaques via IL-1β secretion.
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巨噬细胞中胆固醇的积聚通过IL-1β的分泌推动动脉粥样硬化斑块中的NETsis。
DOI：
10.1093/cvr/cvac189
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发表时间：
2023-05-02
影响因子：
10.8
通讯作者：
中科院分区：
文献类型：
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作者：
Neutrophil extracellular trap formation (NETosis) increases atherosclerotic plaque vulnerability and athero-thrombosis. However, mechanisms promoting NETosis during atherogenesis are poorly understood. We have shown that cholesterol accumulation due to myeloid cell deficiency of the cholesterol transporters ATP Binding Cassette A1 and G1 (ABCA1/G1) promotes NLRP3 inflammasome activation in macrophages and neutrophils and induces prominent NETosis in atherosclerotic plaques. We investigated whether NETosis is a cell-intrinsic effect in neutrophils or is mediated indirectly by cellular crosstalk from macrophages to neutrophils involving IL-1β. We generated mice with neutrophil or macrophage-specific Abca1/g1 deficiency (S100A8CreAbca1fl/flAbcg1fl/fl or CX3CR1CreAbca1fl/flAbcg1fl/fl mice, respectively), and transplanted their bone marrow into low-density lipoprotein receptor knockout mice. We then fed the mice a cholesterol-rich diet. Macrophage, but not neutrophil Abca1/g1 deficiency activated inflammasomes in macrophages and neutrophils, reflected by caspase-1 cleavage, and induced NETosis in plaques. NETosis was suppressed by administering an interleukin (IL)-1β neutralizing antibody. The extent of NETosis in plaques correlated strongly with the degree of neutrophil accumulation, irrespective of blood neutrophil counts, and neutrophil accumulation was decreased by IL-1β antagonism. In vitro, IL-1β or media transferred from Abca1/g1-deficient macrophages increased NETosis in both control and Abca1/Abcg1 deficient neutrophils. This cell-extrinsic effect of IL-1β on NETosis was blocked by an NLRP3 inhibitor. These studies establish a new link between inflammasome-mediated IL-1β production in macrophages and NETosis in atherosclerotic plaques. Macrophage-derived IL-1β appears to increase NETosis both by increasing neutrophil recruitment to plaques and by promoting neutrophil NLRP3 inflammasome activation.
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影响因子：
7.3
作者：
Liu Y;Carmona-Rivera C;Moore E;Seto NL;Knight JS;Pryor M;Yang ZH;Hemmers S;Remaley AT;Mowen KA;Kaplan MJ
通讯作者：
Kaplan MJ
影响因子：
64.5
作者：
Mitroulis I;Ruppova K;Wang B;Chen LS;Grzybek M;Grinenko T;Eugster A;Troullinaki M;Palladini A;Kourtzelis I;Chatzigeorgiou A;Schlitzer A;Beyer M;Joosten LAB;Isermann B;Lesche M;Petzold A;Simons K;Henry I;Dahl A;Schultze JL;Wielockx B;Zamboni N;Mirtschink P;Coskun Ü;Hajishengallis G;Netea MG;Chavakis T
通讯作者：
Chavakis T
影响因子：
5.6
作者：
Mechelke T;Wittig F;Ramer R;Hinz B
通讯作者：
Hinz B
DOI：
10.1161/atvbaha.113.301627
发表时间：
2013-08
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Borissoff JI;Joosen IA;Versteylen MO;Brill A;Fuchs TA;Savchenko AS;Gallant M;Martinod K;Ten Cate H;Hofstra L;Crijns HJ;Wagner DD;Kietselaer BLJH
通讯作者：
Kietselaer BLJH
影响因子：
2.2
作者：
Abram CL;Roberge GL;Hu Y;Lowell CA
通讯作者：
Lowell CA