Commitment to glycolysis sustains survival of NO-producing inflammatory dendritic cells

被引：430

作者：

Everts, Bart ^{[2
]}

Amiel, Eyal ^{[2
]}

van der Windt, Gerritje J. W. ^{[2
]}

Freitas, Tori C. ^{[2
]}

Chott, Robert

Yarasheski, Kevin E.

Pearce, Erika L. ^{[2
]}

Pearce, Edward J. ^{[1
,2
]}

机构：

[1] Washington Univ, Sch Med, Dept Pathol & Immunol, Div Immunobiol, St Louis, MO 63110 USA

[2] Trudeau Inst Inc, Saranac Lake, NY 12983 USA

来源：

BLOOD | 2012年 / 120卷 / 07期

基金：

美国国家卫生研究院;

关键词：

NITRIC-OXIDE SYNTHASE; MITOCHONDRIAL RESPIRATORY-CHAIN; GLUCOSE-METABOLISM; ACTIVATED MACROPHAGES; PROTEIN-KINASE; NADPH OXIDASE; BONE-MARROW; INHIBITION; DYSFUNCTION; INDUCTION;

D O I：

10.1182/blood-2012-03-419747

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

TLR agonists initiate a rapid activation program in dendritic cells (DCs) that requires support from metabolic and bioenergetic resources. We found previously that TLR signaling promotes aerobic glycolysis and a decline in oxidative phosphorylation (OXHPOS) and that glucose restriction prevents activation and leads to premature cell death. However, it remained unclear why the decrease in OXPHOS occurs under these circumstances. Using real-time metabolic flux analysis, in the present study, we show that mitochondrial activity is lost progressively after activation by TLR agonists in inflammatory blood monocyte-derived DCs that express inducible NO synthase. We found that this is because of inhibition of OXPHOS by NO and that the switch to glycolysis is a survival response that serves to maintain ATP levels when OXPHOS is inhibited. Our data identify NO as a profound metabolic regulator in inflammatory monocyte-derived DCs. (Blood. 2012;120(7):1422-1431)

引用

页码：1422 / 1431

页数：10

共 42 条

[1] Neuronal Nitric Oxide Synthase Modulates Maturation of Human Dendritic Cells [J].