Phosphoethanolamine-complexed C-reactive protein: a pharmacological-like macromolecule that binds to native low-density lipoprotein in human serum.
BACKGROUND
C-reactive protein (CRP) is an acute phase plasma protein. An important binding specificity of CRP is for the modified forms of low-density lipoprotein (LDL) in which the phosphocholine-binding sites of CRP participate. CRP, however, does not bind to native LDL.


METHODS
We investigated the interaction of CRP with native LDL using sucrose density gradient ultracentrifugation.


RESULTS
We found that the blocking of the phosphocholine-binding sites of CRP with phosphoethanolamine (PEt) converted CRP into a potent molecule for binding to native LDL. In the presence of PEt, CRP acquired the ability to bind to fluid-phase purified native LDL. Because purified native LDL may undergo subtle modifications, we also used whole human serum as the source of native LDL. In the presence of PEt, CRP bound to native LDL in serum also. The effect of PEt on CRP was selective for LDL because PEt-complexed CRP did not bind to high-density lipoprotein in the serum.


CONCLUSIONS
The pharmacologic intervention of endogenous CRP by PEt-based compounds, or the use of exogenously prepared CRP-PEt complexes, may turn out to be an effective approach to capture native LDL cholesterol in vivo to prevent the development of atherosclerosis.
Singh
Sanjay K
SK
Department of Pharmacology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
Suresh
Madathilparambil V
MV
Prayther
Deborah C
DC
Moorman
Jonathan P
JP
Rusiñol
Antonio E
AE
Agrawal
Alok
A
D002097:C-Reactive Protein / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood* / Q000302:isolation & purification; D004983:Ethanolamines / Q000097:blood*; D006801:Humans; D011485:Protein Binding
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004983:Ethanolamines; C005448:phosphorylethanolamine; D002097:C-Reactive Protein