Dissociation and Subunit Rearrangement of Membrane-Bound Human C-Reactive Proteins

Wang, Hongwei; Sui, Sen‐Fang

doi:10.1006/bbrc.2001.5733

Cited by 53 publications

(44 citation statements)

References 35 publications

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“…9 This can occur during inflammation, at the surface of apoptotic and necrotic cells, at low pH, in the presence of oxygen radicals or in a proteolytic environment. 11,13,26 Structurally modified CRP, ultimately representing monomeric units, exposes novel binding sites.…”

Section: Discussionmentioning

confidence: 99%

“…7,8 This 125-kDa pentameric form (pCRP) is modified on calcium depletion, heat or urea treatment, surface attachment, by inflammatory conditions, oxidative stress, low pH or by proteases, and dissociates into monomeric units of 23 kDa, termed monomeric CRP (mCRP). [9][10][11] The exact biological functions of pCRP and mCRP are currently unclear. Both mCRP and pCRP bind to damaged cells.…”

mentioning

confidence: 99%

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Monomeric CRP contributes to complement control in fluid phase and on cellular surfaces and increases phagocytosis by recruiting factor H

et al. 2009

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Monomeric CRP contributes to complement control in fluid phase and on cellular surfaces and increases phagocytosis by recruiting factor H

et al. 2009

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“…The CRP induction became detectable only after 6 to 12 hours of incubation, reaching maximal effects at 24 hours, [13][14][15] coinciding with in vitro kinetics of dissociation into subunits. 20 Although CRP clearly enhanced IL-8 and MCP-1 production at 24 hours of culture, it was a significantly less potent inducer of cytokine production than mCRP. These observations suggest that conformational rearrangement of CRP is a prerequisite for activation of HCAECs and that the amounts of mCRP generated from CRP within 4 hours are not sufficient to evoke detectable responses.…”

Section: Khreiss Et Al Loss Of Symmetry In Crp and Inflammation 2019mentioning

confidence: 92%

“…20 These subunits expressing several neoepitopes are referred to as modified or monomeric CRP (mCRP). mCRP antigens were detected in the wall of human normal blood vessels 21 and in inflamed tissues.…”

Section: See P 1914mentioning

confidence: 99%

Conformational Rearrangement in C-Reactive Protein Is Required for Proinflammatory Actions on Human Endothelial Cells

et al. 2004

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Background-C-reactive protein (CRP) has been suggested to actively amplify the inflammatory response underlying coronary heart diseases by directly activating endothelial cells. In this study, we investigated whether loss of the cyclic pentameric structure of CRP, resulting in formation of modified or monomeric CRP (mCRP), is a prerequisite for endothelial cell activation. Methods and Results-We examined the impact of native CRP and mCRP on the production of monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8), key regulators of leukocyte recruitment, and on the expression of intercellular adhesion molecule-1 (ICAM-1), E-selectin, and vascular adhesion molecule-1 (VCAM-1) in human cultured coronary artery endothelial cells (HCAECs). Incubation with mCRP for 4 hours increased MCP-1 and IL-8 secretion and mRNA levels and expression of ICAM-1, E-selectin, and VCAM-1 protein and mRNA. Significant induction occurred at 1 to 5 g/mL, reached a maximum at 30 g/mL, and did not require the presence of serum. Native CRP was without detectable effects at 4 hours, whereas it enhanced cytokine release after a 24-hour incubation. An anti-Fc␥RIII (CD16) but not an anti-Fc␥RII (CD32) antibody produced a 14% to 32% reduction of the mCRP effects (PϽ0.05). mCRP but not CRP evoked phosphorylation of p38 mitogen-activated protein kinase, and inhibition of this kinase with SB 203580 reversed the effects of mCRP. Furthermore, culture of HCAECs in the presence of SB203580 markedly decreased mCRP-stimulated E-selectin and ICAM-1-dependent adhesion of neutrophils to HCAECs (PϽ0.001). Conclusions-Loss of pentameric symmetry in CRP, resulting in formation of mCRP, promotes a proinflammatory HCAEC phenotype through a p38 MAPK-dependent mechanism.

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“…Therefore, the identification of dissociation pathways with a pathophysiological relevance is of paramount importance. The first hint came from the open-ring-like appearance of CRP bound to lipid monolayers when visualized by electron microscopy, arguing for a membrane-induced dissociation [72]. With this observation, we have provided compelling evidence that the lysoPC-dependent, multi-point binding of CRP to model or apoptotic cell membranes can overcome the stabilization effects of calcium and induce a rapid formation of a hybrid state [73].…”

Section: Dissociation Of Crp Localizes the Enhanced Bioactivitiesmentioning

confidence: 81%

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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Dissociation and Subunit Rearrangement of Membrane-Bound Human C-Reactive Proteins

Cited by 53 publications

References 35 publications

Monomeric CRP contributes to complement control in fluid phase and on cellular surfaces and increases phagocytosis by recruiting factor H

Monomeric CRP contributes to complement control in fluid phase and on cellular surfaces and increases phagocytosis by recruiting factor H

Conformational Rearrangement in C-Reactive Protein Is Required for Proinflammatory Actions on Human Endothelial Cells

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

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