Conduct unbecoming: C-reactive protein interactions with a broad range of protein molecules.
BACKGROUND
C-reactive protein (CRP), a pentamer composed of five identical 23-kd subunits, is a member of a highly conserved family of proteins known as pentraxins. CRP has been recognized as a risk factor for the development of both the native and transplant-associated forms of atherosclerosis. Understanding the biology of CRP may be relevant to understanding atherosclerosis development and progression.


METHODS
Using Western-blotting techniques, we examined the interactions between native, monomeric and mutationally and chemically modified CRP and a variety of antibodies, monoclonal and polyclonal.


RESULTS
CRP in its denatured monomeric form, but not in its native pentameric conformation, associates promiscuously with IgG molecules, including normal human IgG, as well as with a number of other proteins. This behavior is intrinsic to CRP and is not noted with other pentraxins such as serum amyloid P component or the long pentraxin, PTX3. Monomeric CRP co-localizes with vitronectin in human heart tissue sections.


CONCLUSIONS
We present these findings as cautionary advice, to indicate that characterization of monomeric CRP can be complicated by the propensity of the molecule to interact with a variety of immunoglobulins and other proteins. We also suggest that it is possible that such interactions could serve to eliminate excess of monomeric CRP and/or to scavenge altered, damaged and denatured proteins. These reactivities may be part of a regulatory mechanism to limit inflammation in the arterial wall.
Boguslawski
George
G
Methodist Research Institute, Clarian Health Partners, Indianapolis, Indiana 46202, USA.
McGlynn
Patrick W
PW
Potempa
Lawrence A
LA
Filep
Janos G
JG
Labarrere
Carlos A
CA
D050197:Atherosclerosis / Q000378:metabolism / Q000503:physiopathology; D001706:Biopsy; D015153:Blotting, Western; D002097:C-Reactive Protein / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D016027:Heart Transplantation / Q000473:pathology; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D008024:Ligands; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D011489:Protein Denaturation; D019096:Vitronectin / Q000378:metabolism*
D007136:Immunoglobulins; D008024:Ligands; D019096:Vitronectin; D002097:C-Reactive Protein