Metabolic Adaptation of Macrophages as Mechanism of Defense against Crystalline Silica.
Metabolic Adaptation of Macrophages as Mechanism of Defense against Crystalline Silica.
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DOI：
10.4049/jimmunol.2000628
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发表时间：
2021-09-15
期刊：
影响因子：
--
通讯作者：
Ortiz LA
中科院分区：
文献类型：
--
作者：
Marrocco A;Frawley K;Pearce LL;Peterson J;O'Brien JP;Mullett SJ;Wendell SG;St Croix CM;Mischler SE;Ortiz LA
Silicosis is a lethal pneumoconiosis for which no therapy is available. Silicosis is a global threat and more than 2.2 million people/year are exposed to silica in the US. The initial response to silica is mediated by innate immunity. Phagocytosis of silica particles by macrophages is followed by recruitment of mitochondria to phagosomes, generation of mitochondrial Reactive-Oxygen-Species (ROS), and cytokine (IL-1β, TNF-α, IFN-β) release. In contrast to lipopolysaccharide (LPS), the metabolic remodeling of silica-exposed macrophages is unclear. This study contrasts mitochondrial and metabolic alterations induced by LPS and silica on macrophages and correlates them with macrophages viability and cytokine production, central to the pathogenesis of silicosis. Using high-resolution respirometer and liquid chromatography-high resolution mass spectrometry (LC-HRMS), we determined the effects of silica and LPS on mitochondrial respiration, and changes in central carbon metabolism of murine macrophage cell lines RAW 264.7 and IC-21. We show that silica induces metabolic reprogramming of macrophages. Silica, as well as LPS, enhances glucose uptake and increases aerobic glycolysis in macrophages. In contrast to LPS, silica affects mitochondria respiration, reducing complex-I and enhancing complex-II activity, to sustain cell viability. These mitochondrial alterations are associated, in silica, but not in LPS-exposed macrophages, with reductions of tricarboxylic-acid cycle (TCA) intermediates, including succinate, itaconate, glutamate, and glutamine. Furthermore, in contrast to LPS, these silica-induced metabolic adaptations do not correlate with IL-1β or TNF-α production, but with the suppressed release of IFN-β. Our data highlights the importance of CII-activity, and TCA-remodeling to macrophage survival and cytokine-mediated inflammation in silicosis.
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影响因子：
29
作者：
Lampropoulou V;Sergushichev A;Bambouskova M;Nair S;Vincent EE;Loginicheva E;Cervantes-Barragan L;Ma X;Huang SC;Griss T;Weinheimer CJ;Khader S;Randolph GJ;Pearce EJ;Jones RG;Diwan A;Diamond MS;Artyomov MN
通讯作者：
Artyomov MN
影响因子：
3.8
作者：
Anderson SE;Shane H;Long C;Marrocco A;Lukomska E;Roberts JR;Marshall N;Fedan JS
通讯作者：
Fedan JS
影响因子：
29
作者：
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通讯作者：
Nijtmans, Leo
影响因子：
4.1
作者：
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通讯作者：
Iacobazzi, Vito
影响因子：
30.5
作者：
通讯作者：
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