Oxidized phospholipid: POVPC binds to platelet-activating-factor receptor on human macrophages. Implications in atherosclerosis.

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Pegorier S, Stengel D, Durand H, Croset M, Ninio E

Oxidized phospholipid: POVPC binds to platelet-activating-factor receptor on human macrophages. Implications in atherosclerosis.

Atherosclerosis. 2006 Oct;188(2):433-43. Epub 2005 Dec 28.

PubMed ID

16386258 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Platelet Activating Factor	Platelet-activating factor receptor	Protein	Humans	Unknown	Not Available	Details

Pharmaco-transcriptomics

Drug	Drug Groups	Gene	Gene ID	Change	Interaction	Chromosome
Platelet Activating Factor	Experimental	AGTR1	185	upregulated	Platelet Activating Factor results in increased expression of AGTR1 mRNA	3q24
Platelet Activating Factor	Experimental	ALOX12	239	upregulated	Platelet Activating Factor results in increased expression of ALOX12 mRNA	17p13.1
Platelet Activating Factor	Experimental	ALOX5	240	upregulated	Platelet Activating Factor results in increased expression of ALOX5 mRNA	10q11.21
Platelet Activating Factor	Experimental	CCR2	729230	upregulated	Platelet Activating Factor results in increased expression of CCR2 mRNA	3p21.31
Platelet Activating Factor	Experimental	CRP	1401	upregulated	Platelet Activating Factor results in increased expression of CRP mRNA	1q23.2
Platelet Activating Factor	Experimental	CX3CR1	1524	upregulated	Platelet Activating Factor results in increased expression of CX3CR1 mRNA	3p22.2
Platelet Activating Factor	Experimental	EGR1	1958	upregulated	Platelet Activating Factor results in increased expression of EGR1 mRNA	5q31.2
Platelet Activating Factor	Experimental	IL1A	3552	upregulated	Platelet Activating Factor results in increased expression of IL1A mRNA	2q14.1
Platelet Activating Factor	Experimental	IL1B	3553	upregulated	Platelet Activating Factor results in increased expression of IL1B mRNA	2q14.1
Platelet Activating Factor	Experimental	MMP13	4322	upregulated	Platelet Activating Factor results in increased expression of MMP13 mRNA	11q22.2
Platelet Activating Factor	Experimental	OLR1	4973	upregulated	Platelet Activating Factor results in increased expression of OLR1 mRNA	12p13.2
Platelet Activating Factor	Experimental	PPARA	5465	downregulated	Platelet Activating Factor results in decreased expression of PPARA mRNA	22q13.31
Platelet Activating Factor	Experimental	PTAFR	5724	upregulated	Platelet Activating Factor results in increased expression of PTAFR mRNA	1p35.3
Platelet Activating Factor	Experimental	PTGS1	5742	upregulated	Platelet Activating Factor results in increased expression of PTGS1 mRNA	9q33.2
Platelet Activating Factor	Experimental	PTGS2	5743	upregulated	Platelet Activating Factor results in increased expression of PTGS2 mRNA	1q31.1
Platelet Activating Factor	Experimental	SELE	6401	upregulated	Platelet Activating Factor results in increased expression of SELE mRNA	1q24.2
Platelet Activating Factor	Experimental	TIMP4	7079	upregulated	Platelet Activating Factor results in increased expression of TIMP4 mRNA	3p25.2
Platelet Activating Factor	Experimental	TNF	7124	upregulated	Platelet Activating Factor results in increased expression of TNF mRNA	6p21.33