A mouse macrophage lipidome.

Published

Journal Article

We report the lipidomic response of the murine macrophage RAW cell line to Kdo(2)-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.

Full Text

Duke Authors

Cited Authors

  • 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; Subramaniam, S

Published Date

  • December 2010

Published In

Volume / Issue

  • 285 / 51

Start / End Page

  • 39976 - 39985

PubMed ID

  • 20923771

Pubmed Central ID

  • 20923771

Electronic International Standard Serial Number (EISSN)

  • 1083-351X

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M110.182915

Language

  • eng