Solid-phase classical complement activation by C-reactive protein (CRP) is inhibited by fluid-phase CRP-C1q interaction
2007 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 352, no 1, 251-258 p.Article in journal (Refereed) Published
C-reactive protein (CRP) interacts with phosphorylcholine (PC), Fcgamma receptors, complement factor C1q and cell nuclear constituents, yet its biological roles are insufficiently understood. The aim was to characterize CRP-induced complement activation by ellipsometry. PC conjugated with keyhole limpet hemocyanin (PC-KLH) was immobilized to cross-linked fibrinogen. A low-CRP serum with different amounts of added CRP was exposed to the PC-surfaces. The total serum protein deposition was quantified and deposition of IgG, C1q, C3c, C4, factor H, and CRP detected with polyclonal antibodies. The binding of serum CRP to PC-KLH dose-dependently triggered activation of the classical pathway. Unexpectedly, the activation was efficiently down-regulated at CRP levels > 150 mg/L. Using radial immunodiffusion, CRP-C1q interaction was observed in serum samples with high CRP concentrations. We propose that the underlying mechanism depends on fluid-phase interaction between C1q and CRP. This might constitute another level of complement regulation, which has implications for systemic lupus erythematosus where CRP is often low despite flare-ups.
Place, publisher, year, edition, pages
Elsevier, 2007. Vol. 352, no 1, 251-258 p.
C-reactive protein; C1q; complement; inflammation; opsonization; pentraxins; systemic lupus erythematosus
Cell and Molecular Biology
IdentifiersURN: urn:nbn:se:oru:diva-56659DOI: 10.1016/j.bbrc.2006.11.013ISI: 000243056700041PubMedID: 17113035ScopusID: 2-s2.0-33751433364OAI: oai:DiVA.org:oru-56659DiVA: diva2:1083500