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

168 Scopus citations

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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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Dennis, E. A., Deems, R. A., Harkewicz, R., Quehenberger, O., Brown, H. A., Milne, S. B., Myers, D. S., Glass, C. K., Hardiman, G., Reichart, D., Merrill, A. H., Sullards, M. C., Wang, E., Murphy, R. C., Raetz, C. R. H., Garrett, T. A., Guan, Z., Ryan, A. C., Russell, D. W., ... Subramaniama, S. (2010). A mouse macrophage lipidome. Journal of Biological Chemistry, 285(51), 39976-39985. https://doi.org/10.1074/jbc.M110.182915