C-reactive protein binds to both oxidized LDL and apoptotic cells through recognition of a common ligand: Phosphorylcholine of oxidized phospholipids.
C-reactive protein (CRP) is an acute-phase protein that binds specifically to phosphorylcholine (PC) as a component of microbial capsular polysaccharide and participates in the innate immune response against microorganisms. CRP elevation also is a major risk factor for cardiovascular disease. We previously demonstrated that EO6, an antioxidized LDL autoantibody, was a T15 clono-specific anti-PC antibody and specifically binds to PC on oxidized phosphatidylcholine (PtC) but not on native PtC. Similarly, EO6 binds apoptotic cells but not viable cells. In addition, such oxidized phospholipids are recognized by macrophage scavenger receptors, implying that these innate immune responses participate in the clearance because of their proinflammatory properties. We now report that CRP binds to oxidized LDL (OxLDL) and oxidized PtC (OxPtC), but does not bind to native, nonoxidized LDL nor to nonoxidized PtC, and its binding is mediated through the recognition of a PC moiety. Reciprocally, CRP binds to PC, which can be competed for by OxLDL and OxPtC but not by native LDL, nonoxidized PtC, or by oxidized phospholipids without the PC headgroup. CRP also binds to apoptotic cells, and this binding is competed for by OxLDL, OxPtC, and PC. These data suggest that CRP binds OxLDL and apoptotic cells by recognition of a PC moiety that becomes accessible as a result of oxidation of PtC molecule. We propose that, analogous to EO6 and scavenger receptors, CRP is a part of the innate immune response to oxidized PC-bearing phospholipids within OxLDL and on the plasma membranes of apoptotic cells.
Chang
Mi-Kyung
MK
Department of Medicine, University of California at San Diego, La Jolla, CA 92093-0682, USA. m7chang@ucsd.edu
Binder
Christoph J
CJ
Torzewski
Michael
M
Witztum
Joseph L
JL
D000941:Antigens / Q000378:metabolism; D017209:Apoptosis; D001323:Autoantibodies / Q000737:chemistry*; D001667:Binding, Competitive; D002097:C-Reactive Protein / Q000737:chemistry / Q000378:metabolism*; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D000939:Epitopes; D006801:Humans; D007118:Immunoassay; D007150:Immunohistochemistry; D019169:Jurkat Cells; D008024:Ligands; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008565:Membrane Proteins; D010100:Oxygen / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D010767:Phosphorylcholine / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000378:metabolism; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
D000941:Antigens; D001323:Autoantibodies; D000939:Epitopes; D008024:Ligands; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D010713:Phosphatidylcholines; D010743:Phospholipids; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C099252:oxidized low density lipoprotein; D010767:Phosphorylcholine; D002097:C-Reactive Protein; D010100:Oxygen