C-reactive protein and annexin A5 bind to distinct sites of negatively charged phospholipids present in oxidized low-density lipoprotein

Arterioscler Thromb Vasc Biol. 2005 Apr;25(4):717-22. doi: 10.1161/01.ATV.0000157979.51673.2c. Epub 2005 Feb 3.

Abstract

Objective: To investigate binding of C-reactive protein (CRP) and annexin A5, 2 proteins with high affinity for negatively charged phospholipids, to oxidized low-density lipoprotein (LDL) and the consequences of these interactions for subsequent binding of oxidized LDL to monocyte/macrophage-like U937 cells.

Methods and results: We found that CRP and annexin A5 at physiological concentrations bind Ca++ dependently to oxidized phosphatidylcholine present in oxidized LDL but not to native LDL. Binding of CRP to oxidized LDL did not interfere with binding of annexin A5, and vice versa. In the presence of 2 to 10 mg/L CRP, binding of 125I-labeled oxidized LDL to undifferentiated U937 cells increased 50% to 100%. This effect was independent of the presence of complement and could be inhibited by irrelevant IgG and by antibodies to CD64 but not by annexin A5. Annexin A5 alone had no effect on binding of oxidized LDL to the cells.

Conclusions: These findings suggest that: (1) CRP and annexin A5 at physiological concentrations bind to distinct sites of negatively charged phospholipids present in oxidized LDL; (2) CRP enhances binding of oxidized LDL to monocytic/macrophage-like cells via Fcgamma receptors; and (3) annexin A5 does not antagonize the CRP-induced enhanced binding of oxidized LDL to U937 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Annexin A5 / metabolism*
  • Antibodies, Monoclonal
  • Binding Sites
  • C-Reactive Protein / metabolism*
  • Electrochemistry
  • Epitopes / immunology
  • Epitopes / metabolism
  • Humans
  • Iodine Radioisotopes
  • Lipoproteins, LDL / chemistry*
  • Lipoproteins, LDL / immunology
  • Lipoproteins, LDL / metabolism*
  • Phagocytes / metabolism
  • Phospholipids / chemistry
  • Phospholipids / metabolism*
  • Receptors, IgG / metabolism
  • U937 Cells

Substances

  • Annexin A5
  • Antibodies, Monoclonal
  • Epitopes
  • Iodine Radioisotopes
  • Lipoproteins, LDL
  • Phospholipids
  • Receptors, IgG
  • oxidized low density lipoprotein
  • C-Reactive Protein