TY - JOUR
T1 - A mouse macrophage lipidome
AU - Dennis, Edward A.
AU - Deems, Raymond A.
AU - Harkewicz, Richard
AU - Quehenberger, Oswald
AU - Brown, H. Alex
AU - Milne, Stephen B.
AU - Myers, David S.
AU - Glass, Christopher K.
AU - Hardiman, Gary
AU - Reichart, Donna
AU - Merrill, Alfred H.
AU - Sullards, M. Cameron
AU - Wang, Elaine
AU - Murphy, Robert C.
AU - Raetz, Christian R H
AU - Garrett, Teresa A.
AU - Guan, Ziqiang
AU - Ryan, Andrea C.
AU - Russell, David W.
AU - McDonald, Jeffrey G.
AU - Thompson, Bonne M.
AU - Shaw, Walter A.
AU - Sud, Manish
AU - Zhao, Yihua
AU - Gupta, Shakti
AU - Maurya, Mano R.
AU - Fahy, Eoin
AU - Subramaniama, Shankar
PY - 2010/12/17
Y1 - 2010/12/17
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M110.182915
DO - 10.1074/jbc.M110.182915
M3 - Article
C2 - 20923771
AN - SCOPUS:78649685767
SN - 0021-9258
VL - 285
SP - 39976
EP - 39985
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 51
ER -