Effect of modified C-reactive protein on complement activation: a possible complement regulatory role of modified or monomeric C-reactive protein in atherosclerotic lesions.
OBJECTIVE
The capacity of human C-reactive protein (CRP) to activate/regulate complement may be an important characteristic that links CRP and inflammation with atherosclerosis. Recent advances suggest that in addition to classical pentameric CRP, a conformationally distinct isoform of CRP, termed modified or monomeric CRP (mCRP), may also play an active role in atherosclerosis. Although the complement activation behavior of CRP has been well established, the capacity of mCRP to interact with and activate the complement cascade is unknown.


RESULTS
mCRP bound avidly to purified C1q, and this binding occurred primarily through collagen-like region of C1q. Fluid phase mCRP inhibited the activation of complement cascade via engaging C1q from binding with other complement activators. In contrast, when immobilized or bound to oxidized or enzymatically modified low-density lipoprotein, mCRP could activate classical complement pathway. Low-level generation of sC5b-9 indicated that the activation largely bypassed the terminal sequence of complement, which appears to involve recruitment of Factor H.


CONCLUSIONS
These results indicate that mCRP can both inhibit and activate the classical complement pathway by binding C1q, depending on whether it is in fluid phase or surface-bound state.
Ji
Shang-Rong
SR
Institute of Biophysics, Lanzhou University, Lanzhou 730000, P. R. China.
Wu
Yi
Y
Potempa
Lawrence A
LA
Liang
Yu-Heng
YH
Zhao
Jing
J
D050197:Atherosclerosis / Q000378:metabolism*; D001665:Binding Sites; D002097:C-Reactive Protein / Q000737:chemistry / Q000378:metabolism*; D003167:Complement Activation; D015922:Complement C1q / Q000737:chemistry / Q000378:metabolism*; D003171:Complement Pathway, Classical; D019281:Dimerization; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation
D008077:Lipoproteins, LDL; D015922:Complement C1q; D002097:C-Reactive Protein