Pentraxin binding to isolated rat liver nuclei

Shephard, Enid G.; Smith, Peter J.; Coetzee, Sandra; Strachan, A F; Beer, Frederick C. de

doi:10.1042/bj2790257

Cited by 11 publications

(5 citation statements)

References 23 publications

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“…In line with our findings of the existence of circulating CRPhistone complexes, the interaction between CRP and histone has been reported previously but with some discrepant findings (13,14,(39)(40)(41). To clarify these discrepancies, we immunofluorescently stained EAhy926 cells with Cy5-CRP and FITC-ahscFv to avoid any nonspecific staining of IgGs.…”

Section: The Mechanism Of Crp Detoxification Is Through Preventing Himentioning

confidence: 49%

Human CRP Defends against the Toxicity of Circulating Histones

Abrams

Zhang

Dart

et al. 2013

The Journal of Immunology

116

131

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C-reactive protein (CRP) is an acute-phase protein that plays an important defensive role in innate immunity against bacterial infection, but it is also upregulated in many noninfectious diseases. The generic function of this highly conserved molecule in diseases that range from infection, inflammation, trauma, and malignancy is not well understood. In this article, we demonstrate that CRP defends the human body against the toxicity of histones released into the circulation after extensive cell death. In vitro, CRP significantly alleviates histone-induced endothelial cell damage, permeability increase, and platelet aggregation. In vivo, CRP rescues mice challenged with lethal doses of histones by inhibiting endothelial damage, vascular permeability, and coagulation activation, as reflected by significant reductions in lung edema, hemorrhage, and thrombosis. In patients, elevation of CRP significantly increases the capacity to neutralize extracellular histones in the circulation. We have also confirmed that CRP interacts with individual histones in vitro and forms CRP–histone complexes in serum from patients with both elevated CRP and histones. CRP is able to compete with phospholipid-containing liposomes for the binding to histones. This explains how CRP prevents histones from integrating into cell membranes, which would otherwise induce calcium influx as the major mechanism of cytotoxicity caused by extracellular histones. Because histone elevation occurs in the acute phase of numerous critical illnesses associated with extensive cell death, CRP detoxification of circulating histones would be a generic host defense mechanism in humans.

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Section: The Mechanism Of Crp Detoxification Is Through Preventing Himentioning

confidence: 49%

Human CRP Defends against the Toxicity of Circulating Histones

Abrams

Zhang

Dart

et al. 2013

The Journal of Immunology

116

131

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“…In addition, binding of SAP to nucleoli was noted for the first time. Despite in vitro results from systems involving separated, purified and/or denatured preparations of chromatin constituents [5][6][7]23], or using modified pentraxins [37], no binding of CRP to chromatin in situ was observed. Binding of SAP and CRP took place independently, to separate structures, and there was no evidence of any interaction between them, in contrast to results reported with CRP immobilized by solidphase capture via antibodies or ligands on plastic surfaces [38].…”

Section: Discussionmentioning

confidence: 99%

Binding of pentraxins to different nuclear structures: C-reactive protein binds to small nuclear ribonucleoprotein particles, serum amyloid P component binds to chromatin and nucleoli

Pepys¹,

Booth²,

Tennent³

et al. 1994

Clinical and Experimental Immunology

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SUMMARYBinding of the human pentraxin plasma proteins, C-reactive protein (CRP) and serum amyloid P component (SAP), to the nuclei of human cells was studied using whole acute phase serum as the source of the proteins and confocal immunofluorescence microscopy. CRP and SAP clearly bound to distinct, different structures. Double staining with MoAbs to the Sm D and Sm B/B' components of small nuclear ribonucleoproteins confirmed that CRP bound exclusively to these particles. As expected, SAP bound to chromatin and, in addition, binding to the nucleolus was observed for the first time. These interactions demonstrated under relatively physiological conditions, with native pentraxins unseparated from serum and with nuclear constituents in situ, are likely to be of functional importance in vivo.Keywords pentraxin nucleus chromatin C-reactive protein serum amyloid P component INTRODUCTIONInteractions between the pentraxins, C-reactive protein (CRP) and serum amyloid P component (SAP) in man, and constituents of cell nuclei are important because they may represent biologically significant roles of this conserved plasma protein family [1,2]. Although it is clear that both CRP [3] and SAP [4] bind to nuclei, there are conflicting reports about their respective specific ligands. This controversy arises in part because of differences in the methods used to demonstrate binding. In particular the use, as test ligands, of isolated purified nuclear constituents immobilized under conditions [5][6][7] in which denaturation is unavoidable [8], and the use of unphysiological buffers [9], may reveal interactions which are unlikely to occur in vivo. We have therefore investigated the binding to nuclei of native CRP and SAP from whole acute-phase serum, and used double label confocal immunofluorescence microscopy [10] for the highest degree of morphological resolution.

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“…74–77 The interaction is Ca 2+ -dependent and involves the PCh-binding site of CRP. 75–77 CRP, however, does not bind chromatin in serum suggesting that this interaction occurs only if CRP or chromatin is deposited at sites of inflammation. 78 …”

Section: Short Pentraxins: Crp and Sapmentioning

confidence: 99%

“…81 The primary role of CRP and SAP is believed to be the disposal of nuclear materials released in the extracellular environment by apoptotic and necrotic cells, thereby preventing the hazard of autoimmunity. 77–79 …”

Section: Short Pentraxins: Crp and Sapmentioning

confidence: 99%

Pattern Recognition by Pentraxins

Agrawal

Singh

Bottazzi

et al. 2009

Advances in Experimental Medicine and Biology

139

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Pentraxins are a family of evolutionarily conserved pattern-recognition proteins that are made up of five identical subunits. Based on the primary structure of the subunit, the pentraxins are divided into two groups: short pentraxins and long pentraxins. C-reactive protein (CRP) and serum amyloid P-component (SAP) are the two short pentraxins. The prototype protein of the long pentraxin group is pentraxin 3 (PTX3). CRP and SAP are produced primarily in the liver while PTX3 is produced in a variety of tissues during inflammation. The main functions of short pentraxins are to recognize a variety of pathogenic agents and then to either eliminate them or neutralize their harmful effects by utilizing the complement pathways and macrophages in the host. CRP binds to modified low-density lipoproteins, bacterial polysaccharides, apoptotic cells, and nuclear materials. By virtue of these recognition functions, CRP participates in the resolution of cardiovascular, infectious, and autoimmune diseases. SAP recognizes carbohydrates, nuclear substances, and amyloid fibrils and thus participates in the resolution of infectious diseases, autoimmunity, and amyloidosis. PTX3 interacts with several ligands, including growth factors, extracellular matrix component and selected pathogens, playing a role in complement activation and facilitating pathogen recognition by phagocytes. In addition, data in gene-targeted mice show that PTX3 is essential in female fertility, participating in the assembly of the cumulus oophorus extra-cellular matrix. PTX3 is therefore a nonredundant component of the humoral arm of innate immunity as well as a tuner of inflammation. Thus, in conjunction with the other components of innate immunity, the pentraxins use their pattern-recognition property for the benefit of the host.

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Pentraxin binding to isolated rat liver nuclei

Cited by 11 publications

References 23 publications

Human CRP Defends against the Toxicity of Circulating Histones

Human CRP Defends against the Toxicity of Circulating Histones

Binding of pentraxins to different nuclear structures: C-reactive protein binds to small nuclear ribonucleoprotein particles, serum amyloid P component binds to chromatin and nucleoli

Pattern Recognition by Pentraxins

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