A Novel Interaction between Complement Inhibitor C4b-binding Protein and Plasminogen That Enhances Plasminogen Activation

Agarwal, Vaibhav; Talens, Simone; Grandits, Alexander M.; Blom, Anna M.

doi:10.1074/jbc.m114.619494

Cited by 19 publications

(12 citation statements)

References 45 publications

(44 reference statements)

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“…In addition, complement inhibitor C4b-binding protein binds plasminogen to create a complex that is present in serum and plasma. Activation of plasminogen by uPA leads to an increase in C4b-binding protein, suggesting that these proteins may interact during acute inflammation (Agarwal et al, 2015).…”

Section: Plasminogen Has a Variety Of Functions That Lead To Inflammatory Regulationmentioning

confidence: 99%

A critical role for plasminogen in inflammation

Baker

Strickland

2020

Journal of Experimental Medicine

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Plasminogen and its active form, plasmin, have diverse functions related to the inflammatory response in mammals. Due to these roles in inflammation, plasminogen has been implicated in the progression of a wide range of diseases with an inflammatory component. In this review, we discuss the functions of plasminogen in inflammatory regulation and how this system plays a role in the pathogenesis of diseases spanning organ systems throughout the body.

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Section: Plasminogen Has a Variety Of Functions That Lead To Inflammatory Regulationmentioning

confidence: 99%

A critical role for plasminogen in inflammation

Baker

Strickland

2020

Journal of Experimental Medicine

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“…In comparison, C4BP with bound PS retains its full ability to inhibit complement [17], but the complex does not interfere with coagulation in a PSmediated manner. On the other hand C4BP itself, particularly the form lacking PS, binds plasminogen and auguments its activation via urokinase-type plasminogen activator [18]. The high affinity complexes between C4BP and PS are formed already intracellularly in the endoplasmatic reticulum and β-chain secretion from cells increases dramatically in the presence of PS.…”

Section: C4bp: the Goodmentioning

confidence: 99%

“…C4BP interacts with plasminogen and while both molecules are able to bind independently to some bacteria such as Streptococcus pneumoniae, these interactions are enhanced when C4BP and plasminogen are present simultaneously [18]. Since C4BP enhances plasminogen activation this may result in generation of larger amounts of plasmin on bacterial surface, leading to further attenuation of deposition of C3, which can be degraded by plasmin [117].…”

Section: C4bp Mediates Invasion and Promotes Adhesion Of Pathogensmentioning

confidence: 99%

C4b-binding protein: The good, the bad and the deadly. Novel functions of an old friend

2016

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C4b-binding protein (C4BP) is best known as a potent soluble inhibitor of the classical and lectin pathways of the complement system. This large 500 kDa multimeric plasma glycoprotein is expressed mainly in the liver but also in lung and pancreas. It consists of several identical 75 kDa α-chains and often also one 40 kDa β-chain, both of which are mainly composed of complement control protein (CCP) domains. Structure-function studies revealed that one crucial binding site responsible for inhibition of complement is located to CCP1-3 of the α-chain. Binding of anticoagulant protein S to the CCP1 of the β-chain provides C4BP with the ability to strongly bind apoptotic and necrotic cells in order to prevent inflammation arising from activation of complement by these cells. Further, C4BP interacts strongly with various types of amyloid and enhances fibrillation of islet amyloid polypeptide secreted from pancreatic beta cells, which may attenuate pro-inflammatory and cytotoxic effects of this amyloid. Full deficiency of C4BP has not been identified but non-synonymous alterations in its sequence have been found in haemolytic uremic syndrome and recurrent pregnancy loss. Furthermore, C4BP is bound by several bacterial pathogens, notably Streptococcus pyogenes, which due to inhibition of complement and enhancement of bacterial adhesion to endothelial cells provides these bacteria with a survival advantage in the host. Thus, depending on the context, C4BP has a protective or detrimental role in the organism.

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“…C4BPB is a protein involved in the regulation of the complement 17 and it influences coagulation 18 . Decreased levels of C4BPB may be associated with the enhanced pro-coagulant activity in high CV risk patients.…”

Section: Discussionmentioning

confidence: 99%

Potential role of new molecular plasma signatures on cardiovascular risk stratification in asymptomatic individuals

Baldán-Martín

López

Corbacho-Alonso

et al. 2018

Sci Rep

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The evaluation of cardiovascular (CV) risk is based on equations derived from epidemiological data in individuals beyond the limits of middle age such as the Framingham and SCORE risk assessments. Lifetime Risk calculator (QRisk®), estimates CV risk throughout a subjects’ lifetime, allowing those. A more aggressive and earlier intervention to be identified and offered protection from the consequences of CV and renal disease. The search for molecular profiles in young people that allow a correct stratification of CV risk would be of great interest to adopt preventive therapeutic measures in individuals at high CV risk. To improve the selection of subjects susceptible to intervention with aged between 30–50 years, we have employed a multiple proteomic strategy to search for new markers of early CV disease or reported CV events and to evaluate their relationship with Lifetime Risk. Blood samples from 71 patients were classified into 3 groups according to their CV risk (healthy, with CV risk factors and with a previously reported CV event subjects) and they were analyzed using a high through quantitative proteomics approach. This strategy allowed three different proteomic signatures to be defined, two of which were related to CV stratification and the third one involved markers of organ damage.

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A Novel Interaction between Complement Inhibitor C4b-binding Protein and Plasminogen That Enhances Plasminogen Activation

Cited by 19 publications

References 45 publications

A critical role for plasminogen in inflammation

A critical role for plasminogen in inflammation

C4b-binding protein: The good, the bad and the deadly. Novel functions of an old friend

Potential role of new molecular plasma signatures on cardiovascular risk stratification in asymptomatic individuals

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