Reactome | oxPL binds LBP

oxPL binds LBP

Stable Identifier

R-HSA-8869683

Type

Reaction [binding]

Species

Homo sapiens

Compartment

extracellular region

ReviewStatus

5/5

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Antibacterial defence involves activation of neutrophils that generate reactive oxygen species (ROS) capable of killing bacteria. The ROS production 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
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
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
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