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.
XB-ART-12181
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.

???displayArticle.pubmedLink??? 10518567
???displayArticle.pmcLink??? PMC18403
???displayArticle.link??? Proc Natl Acad Sci U S A
???displayArticle.grants??? [+]

Species referenced: Xenopus laevis
Genes referenced: camp fn1 nfkb1

References [+] :
An, Molecular cloning of the human Edg2 protein and its identification as a functional cellular receptor for lysophosphatidic acid. 1997, Pubmed