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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:717.)
© 2005 American Heart Association, Inc.

Vascular Biology

C-Reactive Protein and Annexin A5 Bind to Distinct Sites of Negatively Charged Phospholipids Present in Oxidized Low-Density Lipoprotein

Lambertus van Tits; Jacqueline de Graaf; Helga Toenhake; Waander van Heerde; Anton Stalenhoef

From the Department of Medicine (L.v.T., J.d.G., H.T., A.S.), Division of General Internal Medicine and Central Hematology Laboratory (W.v.H.), Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

Correspondence to L.J.H. van Tits, Department of Medicine, Division of General Internal Medicine 564, Radboud University Nijmegen Medical Centre, Geert Grooteplein Zuid 8, 6525 GA, Nijmegen, PO Box 9101, 6500 HB, Nijmegen, the Netherlands. E-mail B.vantits{at}aig.umcn.nl

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 Fc receptors; and (3) annexin A5 does not antagonize the CRP-induced enhanced binding of oxidized LDL to U937 cells.

We investigated interactions of C-reactive protein (CRP), annexin A5, and low-density lipoprotein (LDL) with U937 cells. CRP binds to oxidized LDL, and via subsequent interaction with Fc receptors it enhances binding of the particle to U937 cells. Annexin A5 also binds to oxidized LDL but does not interfere with CRP.

Key Words: annexin • binding • C-reactive protein • Fc receptors • oxidized LDL

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