C‐Reactive Protein Triggers Calcium Signalling in Human Neutrophilic Granulocytes via Fcγ<scp>RII</scp>a in an Allele‐Specific Way

Aas, Vigdis; Sand, Kristin L.; Åsheim, H.-C.; Benestad, Haakon B.; Iversen, Jens-Gustav

doi:10.1111/sji.12049

Cited by 8 publications

(8 citation statements)

References 48 publications

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“…The differential binding of CRP to the R form of Fc γ RIIA results in much stronger responses in PMN and monocytes [89, 91]. Recently it was demonstrated that CRP stimulates neutrophil calcium signaling in an Fc γ RIIA allele-specific manner [92], which is consistent with previous findings [89]. …”

Section: Receptor Bindingsupporting

confidence: 81%

Pentraxins: Structure, Function, and Role in Inflammation

2013

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The pentraxins are an ancient family of proteins with a unique architecture found as far back in evolution as the Horseshoe crab. In humans the two members of this family are C-reactive protein and serum amyloid P. Pentraxins are defined by their sequence homology, their pentameric structure and their calcium-dependent binding to their ligands. Pentraxins function as soluble pattern recognition molecules and one of the earliest and most important roles for these proteins is host defense primarily against pathogenic bacteria. They function as opsonins for pathogens through activation of the complement pathway and through binding to Fc gamma receptors. Pentraxins also recognize membrane phospholipids and nuclear components exposed on or released by damaged cells. CRP has a specific interaction with small nuclear ribonucleoproteins whereas SAP is a major recognition molecule for DNA, two nuclear autoantigens. Studies in autoimmune and inflammatory disease models suggest that pentraxins interact with macrophage Fc receptors to regulate the inflammatory response. Because CRP is a strong acute phase reactant it is widely used as a marker of inflammation and infection.

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Section: Receptor Bindingsupporting

confidence: 81%

Pentraxins: Structure, Function, and Role in Inflammation

2013

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“…Both CRP and SAP can impact neutrophil function via FcγRIIA ligation . CRP can trigger calcium flux and neutrophil degranulation, particularly if neutrophils are primed by exposure to IFN‐γ . This effect is significantly influenced by the FcγRIIA genotype, with FcγRIIA‐R131 markedly more responsive to CRP simulation than FcγRIIA‐H131.…”

Section: Fcγriib and Control Of The Innate Immune System In Autoimmunitymentioning

confidence: 99%

FcγRIIB and autoimmunity

Espéli

Smith

Clatworthy

2015

Immunological Reviews

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Autoimmune diseases are characterized by adaptive immune responses against self-antigens, including humoral responses resulting in the production of autoantibodies. Autoantibodies generate inflammation by activating complement and engaging Fcγ receptors (FcγRs). The inhibitory receptor FcγRIIB plays a central role in regulating the generation of autoantibodies and their effector functions, which include activation of innate immune cells and the cellular arm of the adaptive immune system, via effects on antigen presentation to CD4 T cells. Polymorphisms in FcγRIIB have been associated with susceptibility to autoimmunity but protection against infections in humans and mice. In the last few years, new mechanisms by which FcγRIIB controls the adaptive immune response have been described. Notably, FcγRIIB has been shown to regulate germinal center B cells and dendritic cell migration, with potential impact on the development of autoimmune diseases. Recent work has also highlighted the implication of FcγRIIB on the regulation of the innate immune system, via inhibition of Toll-like receptor- and complement receptor-mediated activation. This review will provide an update on the role of FcγRIIB in adaptive immune responses in autoimmunity, and then focus on their emerging function in innate immunity.

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“…In this respect, a limitation to this work is the use of a single in-vitro concentration to depict the influence of CRP on muscle cell function. However, dose response studies (0-100 µg/ml CRP) investigating the effects of CRP on cell function showed that the amplitude of the physiological response increased with increasing CRP concentration with a maximal response at 50 µg/ ml, a concentration which has been used in several previous studies depicting the influence of CRP on other cell types including endothelial cells and smooth muscle cells [47][48][49]. Our work, established the impact of CRP on a critical physiological endpoint (muscle cell size) using a concentration commonly used to describe the in-vitro effects of CRP on cell function.…”

Section: Discussionmentioning

confidence: 99%

Mechanistic Links Underlying the Impact of C-Reactive Protein on Muscle Mass in Elderly

Wåhlin-Larsson

Wilkinson

Strandberg

et al. 2017

Cell Physiol Biochem

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Background/Aims: Mechanisms underlying the relationship between systemic inflammation and age-related decline in muscle mass are poorly defined. The purpose of this work was to investigate the relationship between the systemic inflammatory marker CRP and muscle mass in elderly and to identify mechanisms by which CRP mediates its effects on skeletal muscle, in-vitro. Methods: Muscle mass and serum CRP level were determined in a cohort of 118 older women (67±1.7 years). Human muscle cells were differentiated into myotubes and were exposed to CRP. The size of myotubes was determined after immunofluorescent staining using troponin. Muscle protein synthesis was assessed using stable isotope tracers and key signalling pathways controlling protein synthesis were determined using western-blotting. Results: We observed an inverse relationship between circulating CRP level and muscle mass (β= -0.646 (95% CI: -0.888, -0.405) p<0.05) and demonstrated a reduction (p < 0.05) in the size of human myotubes exposed to CRP for 72 h. We next showed that this morphological change was accompanied by a CRP-mediated reduction (p < 0.05) in muscle protein fractional synthetic rate of human myotubes exposed to CRP for 24 h. We also identified a CRPmediated increased phosphorylation (p<0.05) of regulators of cellular energy stress including AMPK and downstream targets, raptor and ACC-β, together with decreased phosphorylation of Akt and rpS6, which are important factors controlling protein synthesis. Conclusion: This work established for the first time mechanistic links by which chronic elevation of CRP can contribute to age-related decline in muscle function.

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C‐Reactive Protein Triggers Calcium Signalling in Human Neutrophilic Granulocytes via FcγRIIa in an Allele‐Specific Way

Cited by 8 publications

References 48 publications

Pentraxins: Structure, Function, and Role in Inflammation

Pentraxins: Structure, Function, and Role in Inflammation

FcγRIIB and autoimmunity

Mechanistic Links Underlying the Impact of C-Reactive Protein on Muscle Mass in Elderly

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