H. Alex Brown
Principle Investigator; Professor of Pharmacology, Chemistry, and Biochemistry; Associate Director, VICB;
Last active: 2/12/2015

A mouse macrophage lipidome.

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 CR, 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
J Biol Chem. 2010 285 (51): 39976-85

PMID: 20923771 · PMCID: PMC3000979 · DOI:10.1074/jbc.M110.182915

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.

MeSH Terms (9)

Animals Cell Line Immunity, Innate Inflammation Mediators Lipid Metabolism Lipopolysaccharides Macrophages Mice Toll-Like Receptor 4

Connections (1)

This publication is referenced by other Labnodes entities:

Links