Oxidized phospholipids (OxPL), such as oxidized PAPC (1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine) and its derivates (POVPC and PGPC) are the biologically active components of minimally oxidized LDL. Both fragmented and full-length oxygenated molecules can regulate immune reactions including the activation of inflammation. Pro-inflammatory effects of OxPL include stimulation of endothelial cells to bind monocytes and induction of tissue clotting factor, IL-8, MCP-1, G-CSF and other mediators of atherothrombosis. Anti-inflammatory effects of OxPL are mediated by induction of protective enzymes such as heme oxygenase-1 as well as suppression of innate immune responses to bacterial lipopolysaccharide (LPS) due to inhibition of LPS recognition by LPS-binding protein (LBP) and CD14. It is well-known that oxidized phospholipids play, as immune modulators, an important role in cardiovascular diseases such as atherosclerosis. However, these lipid oxidation products have been suggested to also play a role in many other disease settings. Lipid oxidation products accumulate in inflamed and oxidative damaged tissue, where they are derived from oxidative modification of lipoproteins, but also from membranes of cells undergoing apoptosis. Increased oxidative stress as well as decreased clearance of apoptotic cells has been implied to contribute to accumulation of OxPL in chronically inflamed tissues. It is therefore suggested that OxPLs are also associated with other diseases associated with dyslipidemia such as diabetes, metabolic syndrome, renal insufficiency and fatty liver disease. In addition, in organs which are constantly exposed to oxidative stress, including lung, skin, and eyes, increased levels of OxPL are suggested to contribute to inflammatory conditions. In theory, treatment with OxPL neutralizing antibodies can be used to prevent or reverse these diseases. The anti-OxPL antibody HM1142 is able to recognize the OxPL derivates POVPC and PGPC.
Functional studies, Immuno assays, Paraffin sections, Western blot
- FS: antibody 10C12 demonstrated potent OxPL neutralizing activity in vitro and the ability to inhibit macrophage accumulation within arteries of Apoe–/– mice fed a Western diet for 4 weeks. 10C12 treatment caused a 40% decrease in lipid accumulation within aortas of secreted IgM deficient, sIgM–/–Apoe–/–, mice fed a low-fat diet, when the antibody was administrated between 32-40 weeks of age. (Ref.1).
- IHC-P: Staining was done on 5 μm crosssections of human autopsy samples using 10C12 (Ref.1).
Dilutions to be used depend on detection system applied. It is recommended that users test the reagent and determine their own optimal dilutions. The typical starting working dilution is 1:50.