Pathway-oriented profiling of lipid mediators in macrophages

Kita, Yoshiaki; Takahashi, Toshie; Uozumi, Naonori; Nallan, Laxman; Gelb, Michael H.; Shimizu, Takao

doi:10.1016/j.bbrc.2005.03.055

Cited by 37 publications

(30 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This was found both in early work (20) and in recent lipidomic analyses (21)(22)(23)(24). Likewise, eosinophils (25)(26)(27) and mast cells (28)(29)(30)(31)(32) produce mainly LTC 4 , but apparently no or only small amounts of LTD 4 .…”

Section: Timeline Of Cell Culture and Coculturementioning

confidence: 56%

Pulmonary epithelial cancer cells and their exosomes metabolize myeloid cell-derived leukotriene C4 to leukotriene D4

Lukić

Jie

Idborg

et al. 2016

Journal of Lipid Research

View full text Add to dashboard Cite

Leukotrienes (LTs) are mediators of inflammation (1) formed by immune cells in response to pathogens or danger signals. When cells are stimulated, cytosolic phospholipase A 2  (cPLA 2 ) and 5-lipoxygenase (LO) migrate to the nuclear membrane, arachidonic acid (AA) is released from nuclear membrane phospholipids, and LTA 4 is produced (2). Efficient translocation and activation of 5-LO requires two scaffold proteins, 5-LO activating protein (FLAP) and coactosin-like protein (CLP) (3). LTA 4 is then further metabolized by cytosolic LTA 4 hydrolase to LTB 4 , or by LTC 4 synthase (LTC 4 S) to LTC 4 . LTC 4 S is primarily located at the nuclear membrane together with FLAP, and both proteins are members of the family of membrane bound proteins involved in eicosanoid and glutathione metabolism (MAPEG). LTC 4 and its metabolites, LTD 4 and LTE 4 , are jointly referred to as the cysteinyl LTs (CysLTs). CysLTs elicit edema formation, mucus secretion, and smooth muscle contraction, as well as eosinophil trafficking and tissue remodeling, and thus contribute to symptoms in several chronic inflammatory diseases, such as asthma (4). There are at least three different receptors for the CysLTs; in the lung, bronchoconstriction and other effects are mediated via CysLT1. LTD 4 has a 10-to 50-fold higher potency for activation of CysLT1 compared with LTC 4 , while LTE 4 is the least active (5, 6). Thus, metabolism of LTC 4 to LTD 4 may have a considerable impact on CysLT1-mediated effects, also depending on further conversion to LTE 4 . Abstract Leukotrienes (LTs

show abstract

Section: Timeline Of Cell Culture and Coculturementioning

confidence: 56%

Pulmonary epithelial cancer cells and their exosomes metabolize myeloid cell-derived leukotriene C4 to leukotriene D4

Lukić

Jie

Idborg

et al. 2016

Journal of Lipid Research

View full text Add to dashboard Cite

show abstract

“…Different LTC 4 synthesis capacities for different types of Mfs have been described before. High LTC 4 biosynthesis was observed for resident mouse peritoneal Mfs, which produced about 3-fold more LTC 4 compared with thioglycolateelicited cells (9). A subset of Mfs fluorescence-activated cell sorted from mouse lung tumors (MacA, representing resident alveolar Mfs) produced LTC 4 (13).…”

Section: Discussionmentioning

confidence: 98%

GM‐CSF– and M‐CSF–primed macrophages present similar resolving but distinct inflammatory lipid mediator signatures

et al. 2017

View full text Add to dashboard Cite

M1 and M2 activated macrophages (Mfs) have different roles in inflammation. Because pathogens may first encounter resting cells, we investigated lipid mediator profiles prior to full activation. Human monocytes were differentiated with granulocyte Mf colony-stimulating factor (GM-CSF) or Mf colony-stimulating factor (M-CSF), which are known to prime toward M1 or M2 phenotypes, respectively. Lipid mediators released during resting conditions and produced in response to bacterial stimuli (LPS/N-formylmethionyl-leucyl-phenylalanine or peptidoglycan) were quantified by liquid chromatography-mass spectrometry. In resting conditions, both Mf phenotypes released primarily proresolving lipid mediators (prostaglandin E 2 metabolite, lipoxin A 4 , and 18-hydroxyeicosapentaenoic acid). A striking shift toward proinflammatory eicosanoids was observed when the same cells were exposed (30 min) to bacterial stimuli: M-CSF Mfs produced considerably more 5-lipoxygenase products, particularly leukotriene C 4 , potentially linked to M2 functions in asthma. Prostaglandins were formed by both Mf types. In the M-CSF cells, there was also an enhanced release of arachidonic acid and activation of cytosolic phospholipase A 2 . However, GM-CSF cells expressed higher levels of 5-lipoxygenase and 5-lipoxygenase-activating protein, and in ionophore incubations these cells also produced the highest levels of 5-hydroxyeicosatetraenoic acid. In summary, GM-CSF and M-CSF Mfs displayed similar proresolving lipid mediator formation in resting conditions but shifted toward different proinflammatory eicosanoids upon bacterial stimuli. This demonstrates that preference for specific eicosanoid pathways is primed by CSFs before full M1/M2 activation.-Lukic, A., Larssen, P., Fauland, A., Samuelsson, B., Wheelock, C. E., Gabrielsson, S., Radmark, O. GM-CSF-and M-CSF-primed macrophages present similar resolving but distinct inflammatory lipid mediator signatures. FASEB J. 31, 4370-4381 (2017). www.fasebj.orgMacrophages (Mfs) orchestrate the inflammatory process from early onset to the resolution phase (1, 2). A major issue in Mf biology is to characterize functional phenotypes, currently described as a heterogeneous spectrum of activated states, from M1 to M2 (3, 4). Stimulating factors, such as cytokines and pathogens, can induce specific phenotypes: originally IFN-g + LPS activation resulted in a proinflammatory M1 state, whereas IL-4 activation induced the alternatively activated M2 state. Polarized cells express distinct markers, such as transcription factors, cytokines, and surface markers; these are the main tools to define Mf phenotypes. A number of transcripts have been reported to differ between M1 and M2 Mfs, including mRNAs for enzymes involved in eicosanoid metabolism (5).Eicosanoids originate from arachidonic acid (AA), released from membrane phospholipids by phospholipases, typically cytosolic phospholipase A 2 (cPLA 2 ) (6). Free AA is further metabolized via 3 enzymatic pathways: lipoxygenase (LO), cyclooxygenase (COX), and cyto...

show abstract

“…In the present study, we profiled the eicosanoid production of rat hippocampal tissues during KA-induced seizure using the LC-ESI-MS/MS multiple quantification method (13,14). One of the advantages Control, hippocampal tissues of salineinjected (intraperitoneal) rats were immediately dissected; KA, hippocampal tissues were dissected 3 h after KA administration (intraperitoneal).…”

Section: Discussionmentioning

confidence: 99%

“…In the present study, we profiled the eicosanoid production in the rat hippocampus during KA-induced seizure. Taking advantages of the simultaneous quantification method using liquid chromatographyelectrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) (13,14), we carried out a comprehensive analysis of lipid mediators in the rat hippocampal tissues. The time course of COX-2 up-regulation and the profile of lipid mediator production suggested a dual phase regulatory mechanism; a direct KA action may cause a transient burst PG production in the initial phase, whereas increased COX-2 levels mediate the late phase production under limited arachidonic acid supply.…”

mentioning

confidence: 99%

Profiling of Eicosanoid Production in the Rat Hippocampus during Kainic Acid-induced Seizure

Yoshikawa¹,

Kita²,

Kishimoto³

et al. 2006

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Pathway-oriented profiling of lipid mediators in macrophages

Cited by 37 publications

References 32 publications

Pulmonary epithelial cancer cells and their exosomes metabolize myeloid cell-derived leukotriene C4 to leukotriene D4

Pulmonary epithelial cancer cells and their exosomes metabolize myeloid cell-derived leukotriene C4 to leukotriene D4

GM‐CSF– and M‐CSF–primed macrophages present similar resolving but distinct inflammatory lipid mediator signatures

Profiling of Eicosanoid Production in the Rat Hippocampus during Kainic Acid-induced Seizure

Contact Info

Product

Resources

About