oxPL binds CD14

Stable Identifier
R-HSA-8869694
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

The generation of reactive oxygen species is a central feature of inflammation that results in the oxidation of host phospholipids. Endogenously formed oxidized phospholipids, such as 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine (OxPAPC), have been shown to inhibit TLR4- & TLR2-mediated signaling induced by bacterial lipopeptide or lipopolysaccharide (LPS) in various human cells (Bochkov VN et al., 2002; von Schlieffen E et al., 2009). Oxidized phospholipids were found to bind LPS binding protein (LBP) and soluble CD14 suggesting that the binding prevented recognition of LPS by these proteins thus preventing recognition of LPS and activation of TLR4 (Erridge C et al., 2008; von Schlieffen E et al., 2009). In addition, oxPAPC protected mice treated with a lethal dose of LPS (Bochkov VN et al., 2002). Thus, oxidized phospholipids may function as a negative feedback to blunt innate immune responses.

Literature References
PubMed ID Title Journal Year
12214235 Protective role of phospholipid oxidation products in endotoxin-induced tissue damage

Bochkov, VN, Kadl, A, Huber, J, Gruber, F, Binder, BR, Leitinger, N

Nature 2002
18559343 Oxidized phospholipid inhibition of toll-like receptor (TLR) signaling is restricted to TLR2 and TLR4: roles for CD14, LPS-binding protein, and MD2 as targets for specificity of inhibition

Erridge, C, Kennedy, S, Spickett, CM, Webb, DJ

J. Biol. Chem. 2008
19112167 Multi-hit inhibition of circulating and cell-associated components of the toll-like receptor 4 pathway by oxidized phospholipids

von Schlieffen, E, Oskolkova, OV, Schabbauer, G, Gruber, F, Bluml, S, Genest, M, Kadl, A, Marsik, C, Knapp, S, Chow, J, Leitinger, N, Binder, BR, Bochkov, VN

Arterioscler. Thromb. Vasc. Biol. 2009
Participants
Participant Of
Orthologous Events
Authored
Reviewed