Oxidized phospholipid: POVPC binds to platelet-activating-factor receptor on human macrophages. Implications in atherosclerosis.
Atherosclerosis as a chronic inflammatory disease resulting from the imbalance of the pro- and anti-inflammatory factors in the vessel wall. PAF and PAF-like oxidized phospholipids generated upon LDL oxidation in the intima of the arteries may interact with infiltrated monocytes/macrophages and lead to the alteration of gene expression patterns accompanied by an impaired production of chemokines, interleukins and proteolytic and lipolytic enzymes. The aim of this study was to evaluate the binding capacity of the major component of PAF-like oxidized phospholipids, namely the 1-palmitoyl-2-oxovaleroyl-sn-glycero-3-phosphorylcholine (POVPC) to PAF-receptor (PAF-R) on the surface of human monocytes/macrophages and to further characterize the gene expression induced by such binding. We show that, POVPC binds to cultured human macrophages via PAF-R and transduces the signals leading to the intracellular Ca(2+) fluxes and modifies the transcription levels of numerous pro-inflammatory and pro-atherogenic genes. Although a some similarity of the gene expression patterns was observed when macrophages were activated with POVPC versus PAF, we observed that only POVPC treatment induced a several-fold activation of IL-8 gene. In turn, only PAF activated PAF-R, matrix metalloproteinase-13 and 15-lipoxygenase mRNA accumulation. Thus, we suggest, that POVPC signals in mature macrophages only in part through the PAF-R, a part of its effects may involve other receptors.
Pégorier
Sophie
S
INSERM U525, Université Pierre et Marie Curie (UPMC-Paris 6), Faculté de Médecine Pierre et Marie Curie, Paris, France.
Stengel
Dominique
D
Durand
Hervé
H
Croset
Martine
M
Ninio
Ewa
E
D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism*; D002478:Cells, Cultured; D017931:DNA Primers; D005786:Gene Expression Regulation; D006801:Humans; D007118:Immunoassay; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D010742:Phospholipid Ethers / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011485:Protein Binding; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D014316:Tritium
C400184:1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphorylcholine; D017931:DNA Primers; D016209:Interleukin-8; D010742:Phospholipid Ethers; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D014316:Tritium; D001093:Arachidonate 15-Lipoxygenase; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13