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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:337.)
© 2009 American Heart Association, Inc.

Editorials

Oxidized Phospholipid Inhibition of LPS-Signaling

A Good Side to the Bad Guys?

Clett Erridge

From the Department of Cardiovascular Sciences, University of Leicester, UK.

Correspondence to Clett Erridge, Department of Cardiovascular Sciences, University of Leicester, Clinical Sciences Wing, Glenfield General Hospital, Leicester, LE3 9QP, UK. E-mail ce55@le.ac.uk

An extract of the first 250 words of the full text is provided, because this article has no abstract.

As chronic inflammatory processes are now understood to underpin the development of atherosclerosis, and oxidative modification of lipids and lipoproteins has long been considered to play a role in this disease, the mechanisms linking lipid peroxidation with inflammatory signaling are a key area of current atherosclerosis research. Oxidized phospholipids (OxPLs) in particular have received considerable attention in this context since their identification as key mediators of the chemokine-inducing properties of moderately oxidized low-density lipoprotein (mmLDL).¹ OxPLs are formed not only during the oxidative modification of LDL, but also within apoptotic cell membranes, and have been shown to accumulate to reach micromolar concentrations in inflamed tissues, such as atheroma.² To date, it has been widely assumed that OxPLs are predominantly proinflammatory mediators, on the basis of their ability to upregulate expression of interleukin (IL)-8 and monocyte chemoattractant protein (MCP)-1 and the binding of monocytes to endothelial cells.² Paradoxically, however, it has also been shown that OxPLs are potent inhibitors of inflammatory signaling induced by bacterial lipopolysaccharide (LPS, endotoxin), considered by immunologists to be a prototypic proinflammatory agent, both in vitro and in vivo.³

See accompanying article on page 356

Bochkov and colleagues were the first to address the potential mechanisms by which OxPLs could inhibit LPS-signaling.³ They showed that the model OxPL oxidized 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphocholine (OxPAPC) inhibited the binding of LPS to the serum proteins LPS-binding protein (LBP) and soluble (s)CD14, both of which serve to enhance the presentation of LPS monomers to MD2, the binding partner of Toll-like receptor . . . [Full Text of this Article]

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Multi-Hit Inhibition of Circulating and Cell-Associated Components of the Toll-Like Receptor 4 Pathway by Oxidized Phospholipids

Elena von Schlieffen, Olga V. Oskolkova, Gernot Schabbauer, Florian Gruber, Stephan Blüml, Melinda Genest, Alexandra Kadl, Claudia Marsik, Sylvia Knapp, Jesse Chow, Norbert Leitinger, Bernd R. Binder, and Valery N. Bochkov
Arterioscler Thromb Vasc Biol 2009 29: 356-362. [Abstract] [Full Text] [PDF]