A Flow Cytometry‐Based Assay for Procoagulant Platelet Polyphosphate

Labberton, Linda; Long, Andy; Gendler, Sandra J.; Snozek, Christine L.H.; Stavrou, Evi X.; Nickel, Katrin F.; Maas, Coen; Blankenberg, Stefan; Hernandez, James S; Renné, Thomas

doi:10.1002/cyto.b.21492

Cited by 18 publications

(12 citation statements)

References 34 publications

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“…This model may also apply to other cells. As mentioned, polyP is abundant in platelets and released upon activation (54, 55, 77). C1-INH is also found in platelets, secreted and deposited on the activated platelet membrane (78).…”

Section: Relevance Of Polyp In Complementmentioning

confidence: 99%

Polyphosphates and Complement Activation

Conway

2019

Front. Med.

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To sustain life in environments that are fraught with risks of life-threatening injury, organisms have developed innate protective strategies such that the response to wounds is rapid and localized, with the simultaneous recruitment of molecular, biochemical, and cellular pathways that limit bleeding and eliminate pathogens and damaged host cells, while promoting effective healing. These pathways are both coordinated and tightly regulated, as their over- or under-activation may lead to inadequate healing, disease, and/or demise of the host. Recent advances in our understanding of coagulation and complement, a key component of innate immunity, have revealed an intriguing linkage of the two systems. Cell-secreted polyphosphate promotes coagulation, while dampening complement activation, discoveries that are providing insights into disease mechanisms and suggesting novel therapeutic strategies.

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Section: Relevance Of Polyp In Complementmentioning

confidence: 99%

Polyphosphates and Complement Activation

Conway

2019

Front. Med.

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“…However, quantification of P i via malachite green assay and 32 P i via radiodetection obtained from hydrolysed polyP has to be interpreted with caution, since microbial contaminations interfered with these assays to detect polyP in human granulocytes in a previous report [update to (53)]. Analysis of in vivo polyP functions is an area of ongoing research and recently a flow cytometry-based assay has been established to quantify the polymer on cell surfaces (54). Table 1 provides a summary of polyP functions in different organisms, cell populations and intracellular compartments.…”

Section: Intracellular Roles Of Polyphosphatementioning

confidence: 99%

Polyphosphate as a Target for Interference With Inflammation and Thrombosis

et al. 2019

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Activated platelets and mast cells expose the inorganic polymer, polyphosphate (polyP) on their surfaces. PolyP initiates procoagulant and proinflammatory reactions and the polymer has been recognized as a therapeutic target for interference with blood coagulation and vascular hyperpermeability. PolyP content and chain length depend on the specific cell type and energy status, which may affect cellular functions. PolyP metabolism has mainly been studied in bacteria and yeast, but its roles in eukaryotic cells and mammalian systems have remained enigmatic. In this review, we will present an overview of polyP functions, focusing on intra- and extracellular roles of the polymer and discuss open questions that emerge from the current knowledge on polyP regulation.

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“…Independent of the size of the individual, polyP monomer polyP, packed into particles potently activates FXII ( 60 ). PolyP is unstable in plasma ( 61 ) and technology to specifically analyze the polymer has been developed ( 62 ). Recently, intravital microscopy visualized release of polyP nanoparticles from platelet dense granules.…”

Section: The Contact System Integrates With Activated Mast Cells Thementioning

confidence: 99%

Factor XII-Driven Inflammatory Reactions with Implications for Anaphylaxis

et al. 2017

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Anaphylaxis is a life-threatening allergic reaction. It is triggered by the release of pro-inflammatory cytokines and mediators from mast cells and basophils in response to immunologic or non-immunologic mechanisms. Mediators that are released upon mast cell activation include the highly sulfated polysaccharide and inorganic polymer heparin and polyphosphate (polyP), respectively. Heparin and polyP supply a negative surface for factor XII (FXII) activation, a serine protease that drives contact system-mediated coagulation and inflammation. Activation of the FXII substrate plasma kallikrein leads to further activation of zymogen FXII and triggers the pro-inflammatory kallikrein–kinin system that results in the release of the mediator bradykinin (BK). The severity of anaphylaxis is correlated with the intensity of contact system activation, the magnitude of mast cell activation, and BK formation. The main inhibitor of the complement system, C1 esterase inhibitor, potently interferes with FXII activity, indicating a meaningful cross-link between complement and kallikrein–kinin systems. Deficiency in a functional C1 esterase inhibitor leads to a severe swelling disorder called hereditary angioedema (HAE). The significance of FXII in these disorders highlights the importance of studying how these processes are integrated and can be therapeutically targeted. In this review, we focus on how FXII integrates with inflammation and the complement system to cause anaphylaxis and HAE as well as highlight current diagnosis and treatments of BK-related diseases.

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A Flow Cytometry‐Based Assay for Procoagulant Platelet Polyphosphate

Cited by 18 publications

References 34 publications

Polyphosphates and Complement Activation

Polyphosphates and Complement Activation

Polyphosphate as a Target for Interference With Inflammation and Thrombosis

Factor XII-Driven Inflammatory Reactions with Implications for Anaphylaxis

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