Tubular staining of modified C-reactive protein in diabetic chronic kidney disease

Schwedler, Susanne; Guderian, Frank; Dämmrich, J.; Potempa, Lawrence A.; Wanner, Christoph

doi:10.1093/ndt/gfg407

Cited by 68 publications

(54 citation statements)

References 24 publications

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“…This is consistent with previous findings and would enable anti-CRP autoantibodies to interfere with biofunctions of mCRP, since these autoantibodies bind mCRP rather than pentameric CRP [27,[29][30][31].…”

Section: Discussionsupporting

confidence: 93%

“…However, since anti-CRP antibodies in SLE are not directed against the circulating pentameric form of CRP but rather to CRP monomers, a more likely pathogenic potential of circulating anti-CRP would be to target tissue-bound monomeric CRP (mCRP) [22]. Such mCRP has been detected in vessels, skeletal muscle, liver and in tissue of chronic renal disease, possibly with extrahepatically produced CRP [29][30][31][32]. The well-known fact that pentameric CRP activates the classical complement pathway, has also been reported to account for mCRP [33][34][35].…”

Section: Introductionmentioning

confidence: 99%

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C-reactive protein, immunoglobulin G and complement co-localize in renal immune deposits of proliferative lupus nephritis

et al. 2013

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

C-reactive protein, immunoglobulin G and complement co-localize in renal immune deposits of proliferative lupus nephritis

et al. 2013

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“…This has led us to propose that the dissociation of the CRP molecule is an activating mechanism that is required for the expression of enhanced bioactivities and is also a buffering mechanism that localizes the actions of mCRP into inflammatory loci to prevent the possible global effects directly induced by large-scale alterations in the serum levels of CRP [73]. Consistent with our proposal, immunohistochemical analyses using highly specific antibodies revealed that mCRP, not CRP, was the major isoform present in local lesions, including atherosclerotic plaques [55,76], diabetic kidneys [77] and stroke neovessels [78].…”

Section: Dissociation Of Crp Localizes the Enhanced Bioactivitiessupporting

confidence: 83%

Regulated conformation changes in C-reactive protein orchestrate its role in atherogenesis

2012

Chin. Sci. Bull.

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C-reactive protein (CRP) is a prototypic human acute phase reactant composed of five identical subunits. Emerging evidence indicates that CRP is not merely a predictor of cardiovascular disease, but may also be a direct mediator. However, the diverse and sometimes contradictory activities of CRP have considerably hampered the attempts to define the exact role of CRP in atherogenesis. Here, we review the multiple layers of regulation of CRP's structure and function, highlighting how local inflammation conditions, such as the abundance of damaged cell membranes and redox homeostasis, can tip the balance of the pro-and antiinflammatory activities of CRP. We propose that the highly controlled interplay between different structural conformations of CRP underlies its intrinsic property as a fine modulator of inflammation and atherogenesis. C-reactive protein, inflammation, atherosclerosis, redox Citation:Ma X, Ji S R, Wu Y. Regulated conformation changes in C-reactive protein orchestrate its role in atherogenesis.

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“…After tissue damage during the acute-phase reaction, the serum concentration of native, pentameric CRP increases while the monomeric tissue form of CRP may also appear. Indeed, mCRP has been shown to be present in the kidneys of diabetic patients in tubular localization 31 and in atherosclerotic plaques in colocalization with complement proteins. 32,33 Once CRP becomes surface-bound to its ligands the binding site for C1q opens on the disc, resulting in activation of the classical complement pathway.…”

Section: Discussionmentioning

confidence: 99%

Studies on the interactions between C‐reactive protein and complement proteins

et al. 2007

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Studies on the interactions between C-reactive protein and complement proteins IntroductionThe classical acute-phase reactant C-reactive protein (CRP) is a pentameric, disc-shaped serum protein.1 Its basic features are the control of inflammation, the stimulation of clearance of damaged cell and tissue components, and the initiation of repair functions.2 CRP shows calcium-dependent affinity for phosphate monoesters, such as phosphatidylcholine, but several other ligands of CRP have been characterized, including damaged cell membranes, small ribonucleoprotein particles, apoptotic cells and fibronectin. Native CRP can undergo subunit dissociation into individual monomeric units, for example upon association with negatively charged lipid monolayers. 4 This modified form of CRP can be produced in vitro by urea chelation, acid treatment, heating or direct immobilization of native CRP onto polystyrene.5 This modified form of CRP (mCRP) has reduced solubility and exhibits different electrophoretic characteristics as the result of a decrease of isoelectric point (pI) from 6Á4 to 5Á4. 6 The structural changes releasing CRP subunits from the pentamer are correlated with expression of a new antigenic reactivity and formation of neo-epitopes. 7 The forms of CRP expressing SummarySeveral studies have investigated the interactions between C-reactive protein (CRP) and various complement proteins but none of them took into consideration the different structural forms of CRP. The aim of our study was to investigate whether the different antigenic forms of CRP are able to bind C1q, to trigger activation of the C1 complex and to study the ability of the various CRP forms to bind complement factor H (FH) and C4b-binding protein (C4BP). Interactions between various CRP forms and complement proteins were analysed in enzyme-linked immunosorbent assay and surface plasmon resonance tests and activation of the C1 complex was followed in a reconstituted system using purified C1q, C1r and C1s in the presence of C1-INH. Native, ligand-unbound CRP activated the classical pathway weakly. After binding to phosphocholine, native CRP bound C1q and significantly activated C1. Native CRP complexed to phosphocholine did not bind the complement regulatory proteins FH and C4BP. After disruption of the pentameric structure of CRP, as achieved by urea-treatment or by site-directed mutagenesis, C1q binding and C1 activation further increased and the ability of CRP to bind complement regulatory proteins was revealed. C1q binds to CRP through its globular head domain. The binding sites on CRP for FH and C4BP seemed to be different from that of C1q. In conclusion, in parallel with the increase in the C1-activating ability of different CRP structural variants, the affinity for complement regulatory proteins also increased, providing the biological basis for limitation of excess complement activation.

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Tubular staining of modified C-reactive protein in diabetic chronic kidney disease

Cited by 68 publications

References 24 publications

C-reactive protein, immunoglobulin G and complement co-localize in renal immune deposits of proliferative lupus nephritis

C-reactive protein, immunoglobulin G and complement co-localize in renal immune deposits of proliferative lupus nephritis

Regulated conformation changes in C-reactive protein orchestrate its role in atherogenesis

Studies on the interactions between C‐reactive protein and complement proteins

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