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

Mihlan, Michael; Stippa, Selina; Józsi, Mihály; Zipfel, Peter F.

doi:10.1038/cdd.2009.103

Cited by 126 publications

(150 citation statements)

References 41 publications

(49 reference statements)

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“…without yeast cells but using yeast extract, whereas FH alone had no effect. Thus, FH enhanced pathogen-induced proinflammatory cytokine release, in contrast to the previously described anti-inflammatory effect when macrophages phagocytosed apoptotic particles (Mihlan et al, 2009). This suggests that FH can positively or negatively modulate the cytokine response of macrophages, depending on the nature of the phagocytosed particle and the additional stimuli mediated by specific receptors.…”

Section: Discussioncontrasting

confidence: 46%

“…FH has recently been shown to bind in part to CR3 on monocytes and down-modulate the C1q-mediated uptake of apoptotic cells (Kang et al, 2012), and it was also shown to enhance the phagocytosis of apoptotic particles and decrease the release of IL-8 and TNF-α by macrophages (Mihlan et al, 2009). Nevertheless, the nature of the FH receptor on mononuclear phagocytes and the role of pathogen-bound FH in the response of macrophages are poorly characterized.…”

Section: Introductionmentioning

confidence: 99%

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Secreted aspartic protease 2 of Candida albicans inactivates factor H and the macrophage factor H-receptors CR3 (CD11b/CD18) and CR4 (CD11c/CD18)

et al. 2015

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The opportunistic pathogenic yeast Candida albicans employs several mechanisms to interfere with the human complement system. This includes the acquisition of host complement regulators, the release of molecules that scavenge complement proteins or block cellular receptors, and the secretion of proteases that inactivate complement components. Furthermore, FH enhanced zymosan-induced production of these cytokines. C. albicans Sap2 cleaved FH, diminishing its complement regulatory activity, and Sap2-treatment resulted in less detectable CR3 and CR4 on macrophages. These data show that FH enhances the activation of human macrophages when bound on C. albicans. However, the fungus can inactivate both FH and its receptors on macrophages by secreting Sap2, which may represent an additional means for C. albicans to evade the host innate immune system.

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Section: Discussioncontrasting

confidence: 46%

Section: Introductionmentioning

confidence: 99%

Secreted aspartic protease 2 of Candida albicans inactivates factor H and the macrophage factor H-receptors CR3 (CD11b/CD18) and CR4 (CD11c/CD18)

et al. 2015

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“…This could indicate that anti-CRP antibodies in HCV patients may partially be targeted against native epitopes of CRP and not to hidden neo-epitopes (monomeric) CRP as is the case in lupus. Potential pathogenic roles for anti-CRP include impaired clearance of immune complexes and apoptotic debris as well as loss of complement-inhibitory effects of CRP in solution [14,[39][40][41][42]; both scenarios could result in advanced damage in targeted organs [16,37,[43][44][45].…”

Section: Discussionmentioning

confidence: 99%

High prevalence of autoantibodies to C-reactive protein in patients with chronic hepatitis C infection: association with liver fibrosis and portal inflammation

et al. 2012

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The presence of autoantibodies against C-reactive protein (anti-CRP) has been reported in association with autoimmunity and histopathology in chronic hepatitis C virus (HCV) infection. Resistin could play a role in the pathogenesis of hepatitis, although results on HCV infection are ambiguous. Here we retrospectively analyzed anti-CRP and resistin levels in the sera of 38 untreated and well-characterized HCV patients at the time of their first liver biopsy. HCV activity and general health were assessed by a physician at least yearly until follow-up ended. Anti-CRP and resistin were also measured in patients with autoimmune hepatitis (AIH) and nonalcoholic fatty liver disease (NAFLD). Anti-CRP antibodies were registered in all HCV patients, whereas only a few AIH (11%) and NAFLD (12%) sera were positive. Anti-CRP levels were related to histopathological severity and were highest in patients with cirrhosis at baseline. Resistin levels were similar in HCV, AIH, and NAFLD patients, but high levels of resistin were associated with early mortality in HCV patients. Neither anti-CRP nor resistin predicted a response to interferon-based therapy or cirrhosis development or was associated with liver-related mortality. We conclude that anti-CRP antibodies are frequently observed in chronic HCV infection and could be a useful marker of advanced fibrosis and portal inflammation.Funding Agencies|Swedish Society for Medical Research||Professor Nanna Svartz Foundation||King Gustaf V 80-Year Foundation||Sweden-America Foundation||County Council of Ostergotland||Clas Groschinsky||byggmastare Olle Engkvist||apotekare Hedberg|

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“…Subsequent studies confirmed the enhanced interactions of mCRP with modified lipoproteins [61] and complement [62][63][64][65][66][67] and further revealed the important contributions of mCRP in promoting non-inflammatory clearance of apoptotic or necrotic cells by controlling complement activation on the cell surface through balanced recruitment of C1q, Factor H and C4bp [64][65][66]. Because inappropriate handling of CRP, including lyophilization [68], storage in the absence of calcium [69] and immobilization onto microtiter wells [60,70], leads to the disruption of the pentameric structure, the reported properties of CRP suffering these technical pitfalls should be re-evaluated with Factor H interaction as a prominent example [60,64,71].…”

Section: The Bioactivities Of Crp Are Dependent On Conformational Statesmentioning

confidence: 75%

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

Cited by 126 publications

References 41 publications

Secreted aspartic protease 2 of Candida albicans inactivates factor H and the macrophage factor H-receptors CR3 (CD11b/CD18) and CR4 (CD11c/CD18)

Secreted aspartic protease 2 of Candida albicans inactivates factor H and the macrophage factor H-receptors CR3 (CD11b/CD18) and CR4 (CD11c/CD18)

High prevalence of autoantibodies to C-reactive protein in patients with chronic hepatitis C infection: association with liver fibrosis and portal inflammation

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

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