Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Proc Natl Acad Sci U S A
1999 Oct 12;9621:12010-5. doi: 10.1073/pnas.96.21.12010.
Show Gene links
Show Anatomy links
Structurally similar oxidized phospholipids differentially regulate endothelial binding of monocytes and neutrophils.
Leitinger N
,
Tyner TR
,
Oslund L
,
Rizza C
,
Subbanagounder G
,
Lee H
,
Shih PT
,
Mackman N
,
Tigyi G
,
Territo MC
,
Berliner JA
,
Vora DK
.
???displayArticle.abstract???
We previously have demonstrated that oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC), a component of minimally modified low density lipoprotein (MM-LDL), activates endothelial cells to bind monocytes. 1-Palmitoyl-2- (5-oxovaleroyl)-sn-glycero-3-phosphorylcholine (POVPC) and 1- palmitoyl-2-glutaroyl-sn-glycero-3-phosphorylcholine (PGPC), which are present in OxPAPC, MM-LDL, and atherosclerotic lesions, were shown to have a major role in the activation of endothelial cells. We now demonstrate that these two highly similar molecules have dramatically different effects on leukocyte endothelial interactions. POVPC is a potent regulator of monocyte-specific endothelial interactions. Treatment of endothelial cells with POVPC increased monocyte binding by inducing the surface expression of the connecting segment 1 domain of fibronectin; no increase in neutrophil binding was observed. In addition, POVPC strongly inhibited lipopolysaccharide-mediated induction of neutrophil binding and expression of E-selectin protein and mRNA. This inhibition was mediated by a protein kinase A-dependent pathway, resulting in down-regulation of NF-kappaB-dependent transcription. In contrast, PGPC induced both monocyte and neutrophil binding and expression of E-selectin and vascular cell adhesion molecule 1. We present evidence to suggest that the two phospholipids act by different novel receptors present in Xenopus laevis oocytes and that POVPC, but not PGPC, stimulates a cAMP-mediated pathway. At concentrations equal to that present in MM-LDL, the effect of POVPC dominates and inhibits PGPC-induced neutrophil binding and E-selectin expression in endothelial cells. In summary, our data provide evidence that both POVPC and PGPC are important regulators of leukocyte-endothelial interactions and that POVPC may play a dominant role in a number of chronic inflammatory processes where oxidized phospholipids are known to be present.
An,
Molecular cloning of the human Edg2 protein and its identification as a functional cellular receptor for lysophosphatidic acid.
1997, Pubmed
An,
Molecular cloning of the human Edg2 protein and its identification as a functional cellular receptor for lysophosphatidic acid.
1997,
Pubmed
Berliner,
Minimally modified low density lipoprotein stimulates monocyte endothelial interactions.
1990,
Pubmed
Berliner,
The role of oxidized lipoproteins in atherogenesis.
1996,
Pubmed
Berliner,
Oxidized lipids in atherogenesis: formation, destruction and action.
1997,
Pubmed
Boie,
Cloning and expression of a cDNA for the human prostanoid IP receptor.
1994,
Pubmed
,
Xenbase
Brostjan,
Glucocorticoids inhibit E-selectin expression by targeting NF-kappaB and not ATF/c-Jun.
1997,
Pubmed
Böyum,
Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g.
1968,
Pubmed
Cybulsky,
Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis.
1991,
Pubmed
De Luca,
cAMP and tumor necrosis factor competitively regulate transcriptional activation through and nuclear factor binding to the cAMP-responsive element/activating transcription factor element of the endothelial leukocyte adhesion molecule-1 (E-selectin) promoter.
1994,
Pubmed
Fei,
A rapid nuclear runoff transcription assay.
1993,
Pubmed
Fogelman,
Modification of the Recalde method for the isolation of human monocytes.
1988,
Pubmed
Gerrity,
The role of the monocyte in atherogenesis: I. Transition of blood-borne monocytes into foam cells in fatty lesions.
1981,
Pubmed
Han,
Alterations in individual molecular species of human platelet phospholipids during thrombin stimulation: electrospray ionization mass spectrometry-facilitated identification of the boundary conditions for the magnitude and selectivity of thrombin-induced platelet phospholipid hydrolysis.
1996,
Pubmed
Honda,
Cloning by functional expression of platelet-activating factor receptor from guinea-pig lung.
1991,
Pubmed
,
Xenbase
Hörkkö,
Antiphospholipid antibodies are directed against epitopes of oxidized phospholipids. Recognition of cardiolipin by monoclonal antibodies to epitopes of oxidized low density lipoprotein.
1996,
Pubmed
Hörkkö,
The epitopes for some antiphospholipid antibodies are adducts of oxidized phospholipid and beta2 glycoprotein 1 (and other proteins).
1997,
Pubmed
Hörkkö,
Monoclonal autoantibodies specific for oxidized phospholipids or oxidized phospholipid-protein adducts inhibit macrophage uptake of oxidized low-density lipoproteins.
1999,
Pubmed
Kume,
Lysophosphatidylcholine, a component of atherogenic lipoproteins, induces mononuclear leukocyte adhesion molecules in cultured human and rabbit arterial endothelial cells.
1992,
Pubmed
Lee,
Sphingosine-1-phosphate as a ligand for the G protein-coupled receptor EDG-1.
1998,
Pubmed
Leitinger,
Role of group II secretory phospholipase A2 in atherosclerosis: 2. Potential involvement of biologically active oxidized phospholipids.
1999,
Pubmed
Lewis,
Cooperativity between two NF-kappa B complexes, mediated by high-mobility-group protein I(Y), is essential for cytokine-induced expression of the E-selectin promoter.
1994,
Pubmed
Liliom,
N-palmitoyl-serine and N-palmitoyl-tyrosine phosphoric acids are selective competitive antagonists of the lysophosphatidic acid receptors.
1996,
Pubmed
,
Xenbase
Luebke,
Identification of a protein that confers calcitonin gene-related peptide responsiveness to oocytes by using a cystic fibrosis transmembrane conductance regulator assay.
1996,
Pubmed
,
Xenbase
Meacock,
Transcription factor-induced, phased bending of the E-selectin promoter.
1994,
Pubmed
Miledi,
Effects of defolliculation on membrane current responses of Xenopus oocytes.
1989,
Pubmed
,
Xenbase
Morandini,
Action of cAMP on expression and release of adhesion molecules in human endothelial cells.
1996,
Pubmed
O'Brien,
Neovascular expression of E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in human atherosclerosis and their relation to intimal leukocyte content.
1996,
Pubmed
Ollivier,
Elevated cyclic AMP inhibits NF-kappaB-mediated transcription in human monocytic cells and endothelial cells.
1996,
Pubmed
Parhami,
Minimally modified low density lipoprotein-induced inflammatory responses in endothelial cells are mediated by cyclic adenosine monophosphate.
1993,
Pubmed
Parhami,
Stimulation of Gs and inhibition of Gi protein functions by minimally oxidized LDL.
1995,
Pubmed
Parry,
Role of cyclic AMP response element-binding protein in cyclic AMP inhibition of NF-kappaB-mediated transcription.
1997,
Pubmed
Pober,
Elevated cyclic AMP inhibits endothelial cell synthesis and expression of TNF-induced endothelial leukocyte adhesion molecule-1, and vascular cell adhesion molecule-1, but not intercellular adhesion molecule-1.
1993,
Pubmed
Qiao,
Involvement of the tyrosinase gene in the deposition of cardiac lipofuscin in mice. Association with aortic fatty streak development.
1993,
Pubmed
Ravandi,
Determination of lipid ester ozonides and core aldehydes by high-performance liquid chromatography with on-line mass spectrometry.
1995,
Pubmed
Ross,
Cell biology of atherosclerosis.
1995,
Pubmed
Sarafian,
bcl-2 expression decreases methyl mercury-induced free-radical generation and cell killing in a neural cell line.
1994,
Pubmed
Shih,
Minimally modified low-density lipoprotein induces monocyte adhesion to endothelial connecting segment-1 by activating beta1 integrin.
1999,
Pubmed
Stühmer,
Electrophysiological recording from Xenopus oocytes.
1992,
Pubmed
,
Xenbase
Watson,
Effect of platelet activating factor-acetylhydrolase on the formation and action of minimally oxidized low density lipoprotein.
1995,
Pubmed
Watson,
Structural identification by mass spectrometry of oxidized phospholipids in minimally oxidized low density lipoprotein that induce monocyte/endothelial interactions and evidence for their presence in vivo.
1997,
Pubmed
Zhong,
The transcriptional activity of NF-kappaB is regulated by the IkappaB-associated PKAc subunit through a cyclic AMP-independent mechanism.
1997,
Pubmed
Zhong,
Phosphorylation of NF-kappa B p65 by PKA stimulates transcriptional activity by promoting a novel bivalent interaction with the coactivator CBP/p300.
1998,
Pubmed