title: Solid-phase classical complement activation by C-reactive protein (CRP) is inhibited by fluid-phase CRP-C1q interaction.
abstract: 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.
authors.affiliation: Division of Rheumatology/AIR, Department of Molecular and Clinical Medicine, Linköping University, SE-581 85 Linköping, Sweden. chrsj@imk.liu.se
authors.forename: Christopher
authors.initials: C
authors.lastname: Sjöwall
authors.forename: Jonas
authors.initials: J
authors.lastname: Wetterö
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Bengtsson
authors.forename: Agneta
authors.initials: A
authors.lastname: Askendal
authors.forename: Gunnel
authors.initials: G
authors.lastname: Almroth
authors.forename: Thomas
authors.initials: T
authors.lastname: Skogh
authors.forename: Pentti
authors.initials: P
authors.lastname: Tengvall
mesh_terms: D002097:C-Reactive Protein / Q000276:immunology* / Q000378:metabolism*; D003167:Complement Activation / Q000187:drug effects / Q000276:immunology*; D015922:Complement C1q / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D010767:Phosphorylcholine / Q000494:pharmacology; D011485:Protein Binding; D012825:Silicon
chemical_list: D007074:Immunoglobulin G; D010767:Phosphorylcholine; D015922:Complement C1q; D002097:C-Reactive Protein; D012825:Silicon