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


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.
van Tits
Lambertus
L
Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen,The Netherlands. B.vantits@aig.umcn.nl
de Graaf
Jacqueline
J
Toenhake
Helga
H
van Heerde
Waander
W
Stalenhoef
Anton
A
D017304:Annexin A5 / Q000378:metabolism*; D000911:Antibodies, Monoclonal; D001665:Binding Sites; D002097:C-Reactive Protein / Q000378:metabolism*; D004563:Electrochemistry; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D010586:Phagocytes / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism; D020298:U937 Cells
D017304:Annexin A5; D000911:Antibodies, Monoclonal; D000939:Epitopes; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL; D010743:Phospholipids; D017452:Receptors, IgG; C099252:oxidized low density lipoprotein; D002097:C-Reactive Protein