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.