A mouse macrophage lipidome

Edward A. Dennis, Raymond A. Deems, Richard Harkewicz, Oswald Quehenberger, H. Alex Brown, Stephen B. Milne, David S. Myers, Christopher K. Glass, Gary Hardiman, Donna Reichart, Alfred H. Merrill, M. Cameron Sullards, Elaine Wang, Robert C. Murphy, Christian R H Raetz, Teresa A. Garrett, Ziqiang Guan, Andrea C. Ryan, David W. Russell, Jeffrey G. McDonaldBonne M. Thompson, Walter A. Shaw, Manish Sud, Yihua Zhao, Shakti Gupta, Mano R. Maurya, Eoin Fahy, Shankar Subramaniama

Research output: Contribution to journalArticle

162 Citations (Scopus)

Abstract

We report the lipidomic response of the murine macrophage RAW cell line to Kdo2-lipid A, the active component of an inflammatory lipopolysaccharide functioning as a selective TLR4 agonist and compactin, a statin inhibitor of cholesterol biosynthesis. Analyses of lipid molecular species by dynamic quantitative mass spectrometry and concomitant transcriptomic measurements define the lipidome and demonstrate immediate responses in fatty acid metabolism represented by increases in eicosanoid synthesis and delayed responses characterized by sphingolipid and sterol biosynthesis. Lipid remodeling of glycerolipids, glycerophospholipids, and prenols also take place, indicating that activation of the innate immune system by inflammatory mediators leads to alterations in a majority of mammalian lipid categories, including unanticipated effects of a statin drug. Our studies provide a systems-level view of lipid metabolism and reveal significant connections between lipid and cell signaling and biochemical pathways that contribute to innate immune responses and to pharmacological perturbations.

Original languageEnglish (US)
Pages (from-to)39976-39985
Number of pages10
JournalJournal of Biological Chemistry
Volume285
Issue number51
DOIs
StatePublished - Dec 17 2010

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Macrophages
Lipids
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Biosynthesis
Anticholesteremic Agents
Glycerophospholipids
Cell signaling
Sphingolipids
Eicosanoids
Immune system
Sterols
Molecular Dynamics Simulation
Lipid Metabolism
Innate Immunity
Metabolism
Mass spectrometry
Lipopolysaccharides
Immune System
Mass Spectrometry
Fatty Acids

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Dennis, E. A., Deems, R. A., Harkewicz, R., Quehenberger, O., Brown, H. A., Milne, S. B., ... Subramaniama, S. (2010). A mouse macrophage lipidome. Journal of Biological Chemistry, 285(51), 39976-39985. https://doi.org/10.1074/jbc.M110.182915

A mouse macrophage lipidome. / Dennis, Edward A.; Deems, Raymond A.; Harkewicz, Richard; Quehenberger, Oswald; Brown, H. Alex; Milne, Stephen B.; Myers, David S.; Glass, Christopher K.; Hardiman, Gary; Reichart, Donna; Merrill, Alfred H.; Sullards, M. Cameron; Wang, Elaine; Murphy, Robert C.; Raetz, Christian R H; Garrett, Teresa A.; Guan, Ziqiang; Ryan, Andrea C.; Russell, David W.; McDonald, Jeffrey G.; Thompson, Bonne M.; Shaw, Walter A.; Sud, Manish; Zhao, Yihua; Gupta, Shakti; Maurya, Mano R.; Fahy, Eoin; Subramaniama, Shankar.

In: Journal of Biological Chemistry, Vol. 285, No. 51, 17.12.2010, p. 39976-39985.

Research output: Contribution to journalArticle

Dennis, EA, Deems, RA, Harkewicz, R, Quehenberger, O, Brown, HA, Milne, SB, Myers, DS, Glass, CK, Hardiman, G, Reichart, D, Merrill, AH, Sullards, MC, Wang, E, Murphy, RC, Raetz, CRH, Garrett, TA, Guan, Z, Ryan, AC, Russell, DW, McDonald, JG, Thompson, BM, Shaw, WA, Sud, M, Zhao, Y, Gupta, S, Maurya, MR, Fahy, E & Subramaniama, S 2010, 'A mouse macrophage lipidome', Journal of Biological Chemistry, vol. 285, no. 51, pp. 39976-39985. https://doi.org/10.1074/jbc.M110.182915
Dennis EA, Deems RA, Harkewicz R, Quehenberger O, Brown HA, Milne SB et al. A mouse macrophage lipidome. Journal of Biological Chemistry. 2010 Dec 17;285(51):39976-39985. https://doi.org/10.1074/jbc.M110.182915
Dennis, Edward A. ; Deems, Raymond A. ; Harkewicz, Richard ; Quehenberger, Oswald ; Brown, H. Alex ; Milne, Stephen B. ; Myers, David S. ; Glass, Christopher K. ; Hardiman, Gary ; Reichart, Donna ; Merrill, Alfred H. ; Sullards, M. Cameron ; Wang, Elaine ; Murphy, Robert C. ; Raetz, Christian R H ; Garrett, Teresa A. ; Guan, Ziqiang ; Ryan, Andrea C. ; Russell, David W. ; McDonald, Jeffrey G. ; Thompson, Bonne M. ; Shaw, Walter A. ; Sud, Manish ; Zhao, Yihua ; Gupta, Shakti ; Maurya, Mano R. ; Fahy, Eoin ; Subramaniama, Shankar. / A mouse macrophage lipidome. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 51. pp. 39976-39985.
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