C-Reactive Protein Binds to Cholesterol Crystals and Co-Localizes with the Terminal Complement Complex in Human Atherosclerotic Plaques

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C-Reactive Protein Binds to Cholesterol Crystals and Co-Localizes with the Terminal Complement Complex in Human Atherosclerotic Plaques. / Pilely, Katrine; Fumagalli, Stefano; Rosbjerg, Anne; Genster, Ninette; Skjoedt, Mikkel-Ole; Perego, Carlo; Ferrante, Angela M R; De Simoni, Maria-Grazia; Garred, Peter.

In: Frontiers in Immunology, Vol. 8, 1040, 2017.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Pilely, K, Fumagalli, S, Rosbjerg, A, Genster, N, Skjoedt, M-O, Perego, C, Ferrante, AMR, De Simoni, M-G & Garred, P 2017, 'C-Reactive Protein Binds to Cholesterol Crystals and Co-Localizes with the Terminal Complement Complex in Human Atherosclerotic Plaques', Frontiers in Immunology, vol. 8, 1040. https://doi.org/10.3389/fimmu.2017.01040

APA

Pilely, K., Fumagalli, S., Rosbjerg, A., Genster, N., Skjoedt, M-O., Perego, C., ... Garred, P. (2017). C-Reactive Protein Binds to Cholesterol Crystals and Co-Localizes with the Terminal Complement Complex in Human Atherosclerotic Plaques. Frontiers in Immunology, 8, [1040]. https://doi.org/10.3389/fimmu.2017.01040

Vancouver

Pilely K, Fumagalli S, Rosbjerg A, Genster N, Skjoedt M-O, Perego C et al. C-Reactive Protein Binds to Cholesterol Crystals and Co-Localizes with the Terminal Complement Complex in Human Atherosclerotic Plaques. Frontiers in Immunology. 2017;8. 1040. https://doi.org/10.3389/fimmu.2017.01040

Author

Pilely, Katrine ; Fumagalli, Stefano ; Rosbjerg, Anne ; Genster, Ninette ; Skjoedt, Mikkel-Ole ; Perego, Carlo ; Ferrante, Angela M R ; De Simoni, Maria-Grazia ; Garred, Peter. / C-Reactive Protein Binds to Cholesterol Crystals and Co-Localizes with the Terminal Complement Complex in Human Atherosclerotic Plaques. In: Frontiers in Immunology. 2017 ; Vol. 8.

Bibtex

@article{19feceef7c4647b4b8441aaa442209f9,
title = "C-Reactive Protein Binds to Cholesterol Crystals and Co-Localizes with the Terminal Complement Complex in Human Atherosclerotic Plaques",
abstract = "Inflammation is a part of the initial process leading to atherosclerosis and cholesterol crystals (CC), found in atherosclerotic plaques, which are known to induce complement activation. The pentraxins C-reactive protein (CRP), long pentraxin 3 (PTX3), and serum amyloid P component (SAP) are serum proteins associated with increased risk of cardiovascular events and these proteins have been shown to interact with the complement system. Whether the pentraxins binds to CC and mediate downstream complement-dependent inflammatory processes remains unknown. Binding of CRP, PTX3, and SAP to CC was investigated in vitro by flow cytometry and fluorescence microscopy. CRP, PTX3, and SAP bound to CC in a concentration-dependent manner. CRP and PTX3 interacted with the complement pattern recognition molecule C1q on CC by increasing the binding of both purified C1q and C1q in plasma. However, CRP was the strongest mediator of C1q binding and also the pentraxin that most potently elevated C1q-mediated complement activation. In a phagocytic assay using whole blood, we confirmed that phagocytosis of CC is complement dependent and initiated by C1q-mediated activation. The pathophysiological relevance of the in vitro observations was examined in vivo in human atherosclerotic plaques. CRP, PTX3, and SAP were all found in atherosclerotic plaques and were located mainly in the cholesterol-rich necrotic core, but co-localization with the terminal C5b-9 complement complex was only found for CRP. In conclusion, this study identifies CRP as a strong C1q recruiter and complement facilitator on CC, which may be highly relevant for the development of atherosclerosis.",
keywords = "Journal Article",
author = "Katrine Pilely and Stefano Fumagalli and Anne Rosbjerg and Ninette Genster and Mikkel-Ole Skjoedt and Carlo Perego and Ferrante, {Angela M R} and {De Simoni}, Maria-Grazia and Peter Garred",
year = "2017",
doi = "10.3389/fimmu.2017.01040",
language = "English",
volume = "8",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Research Foundation",

}

RIS

TY - JOUR

T1 - C-Reactive Protein Binds to Cholesterol Crystals and Co-Localizes with the Terminal Complement Complex in Human Atherosclerotic Plaques

AU - Pilely, Katrine

AU - Fumagalli, Stefano

AU - Rosbjerg, Anne

AU - Genster, Ninette

AU - Skjoedt, Mikkel-Ole

AU - Perego, Carlo

AU - Ferrante, Angela M R

AU - De Simoni, Maria-Grazia

AU - Garred, Peter

PY - 2017

Y1 - 2017

N2 - Inflammation is a part of the initial process leading to atherosclerosis and cholesterol crystals (CC), found in atherosclerotic plaques, which are known to induce complement activation. The pentraxins C-reactive protein (CRP), long pentraxin 3 (PTX3), and serum amyloid P component (SAP) are serum proteins associated with increased risk of cardiovascular events and these proteins have been shown to interact with the complement system. Whether the pentraxins binds to CC and mediate downstream complement-dependent inflammatory processes remains unknown. Binding of CRP, PTX3, and SAP to CC was investigated in vitro by flow cytometry and fluorescence microscopy. CRP, PTX3, and SAP bound to CC in a concentration-dependent manner. CRP and PTX3 interacted with the complement pattern recognition molecule C1q on CC by increasing the binding of both purified C1q and C1q in plasma. However, CRP was the strongest mediator of C1q binding and also the pentraxin that most potently elevated C1q-mediated complement activation. In a phagocytic assay using whole blood, we confirmed that phagocytosis of CC is complement dependent and initiated by C1q-mediated activation. The pathophysiological relevance of the in vitro observations was examined in vivo in human atherosclerotic plaques. CRP, PTX3, and SAP were all found in atherosclerotic plaques and were located mainly in the cholesterol-rich necrotic core, but co-localization with the terminal C5b-9 complement complex was only found for CRP. In conclusion, this study identifies CRP as a strong C1q recruiter and complement facilitator on CC, which may be highly relevant for the development of atherosclerosis.

AB - Inflammation is a part of the initial process leading to atherosclerosis and cholesterol crystals (CC), found in atherosclerotic plaques, which are known to induce complement activation. The pentraxins C-reactive protein (CRP), long pentraxin 3 (PTX3), and serum amyloid P component (SAP) are serum proteins associated with increased risk of cardiovascular events and these proteins have been shown to interact with the complement system. Whether the pentraxins binds to CC and mediate downstream complement-dependent inflammatory processes remains unknown. Binding of CRP, PTX3, and SAP to CC was investigated in vitro by flow cytometry and fluorescence microscopy. CRP, PTX3, and SAP bound to CC in a concentration-dependent manner. CRP and PTX3 interacted with the complement pattern recognition molecule C1q on CC by increasing the binding of both purified C1q and C1q in plasma. However, CRP was the strongest mediator of C1q binding and also the pentraxin that most potently elevated C1q-mediated complement activation. In a phagocytic assay using whole blood, we confirmed that phagocytosis of CC is complement dependent and initiated by C1q-mediated activation. The pathophysiological relevance of the in vitro observations was examined in vivo in human atherosclerotic plaques. CRP, PTX3, and SAP were all found in atherosclerotic plaques and were located mainly in the cholesterol-rich necrotic core, but co-localization with the terminal C5b-9 complement complex was only found for CRP. In conclusion, this study identifies CRP as a strong C1q recruiter and complement facilitator on CC, which may be highly relevant for the development of atherosclerosis.

KW - Journal Article

U2 - 10.3389/fimmu.2017.01040

DO - 10.3389/fimmu.2017.01040

M3 - Journal article

C2 - 28900428

VL - 8

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

M1 - 1040

ER -

ID: 185718472