Heparan Sulfate Proteoglycans Mediate Factor XIIa Binding to the Cell Surface

Wujak, Lukasz; Didiášová, Miroslava; Zakrzewicz, Dariusz; Frey, Helena; Schaefer, Liliana; Wygrecka, Małgorzata

doi:10.1074/jbc.m114.606343

Cited by 23 publications

(13 citation statements)

References 48 publications

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“…However, when the local Zn 2+ concentration is sufficiently high after cell activation of platelets, leukocytes or endothelial cells, FXII will replace HK on the endothelium [13]. Factor XII also interacts with heparan sulfate on cells with micromolar affinity [14]. Factor XII stimulates cell growth in cultured cells The CAS consists of factor XII (FXII) auto-activating on surfaces (biologic or artificial) to form FXIIa, which then reciprocally activates prekallikrein (PK) to form plasma kallikrein (KAL).…”

Section: The Protein Componentsmentioning

confidence: 99%

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The contact activation and kallikrein/kinin systems: pathophysiologic and physiologic activities

Schmaier

2016

Journal of Thrombosis and Haemostasis

310

370

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Summary. The contact activation system (CAS) and kallikrein/kinin system (KKS) are older recognized biochemical pathways that include several proteins that skirt the fringes of the blood coagulation, fibrinolytic, complement and renin-angiotensin fields. These proteins initially were proposed as part of the hemostatic pathways because their deficiencies are associated with prolonged clinical assays. However, the absence of bleeding states with deficiencies of factor XII (FXII), prekallikrein (PK) and high-molecular-weight kininogen indicates that the CAS and KKS do not contribute to hemostasis. Since the discovery of the Hageman factor 60 years ago much has been learned about the biochemistry, cell biology and animal physiology of these proteins. The CAS is a pathophysiologic surface defense mechanism against foreign proteins, organisms and artificial materials. The KKS is an inflammatory response mechanism. Targeting their activation through FXIIa or plasma kallikrein inhibition when blood interacts with the artificial surfaces of modern interventional medicine or in acute attacks of hereditary angioedema restores vascular homeostasis. FXII/ FXIIa and products that arise with PK deficiency also offer novel ways to reduce arterial and venous thrombosis without an effect on hemostasis. In summary, there is revived interest in the CAS and KKS due to better understanding of their activities. The new appreciation of these systems will lead to several new therapies for a variety of medical disorders.

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Section: The Protein Componentsmentioning

confidence: 99%

“…In physiologic states, FXII is a growth factor promoting vascular health and this function is independent of its catalytic and contact activation ability. It also promotes lung fibroblast proliferation in idiopathic pulmonary fibrosis [14].…”

Section: The Protein Componentsmentioning

confidence: 99%

The contact activation and kallikrein/kinin systems: pathophysiologic and physiologic activities

Schmaier

2016

Journal of Thrombosis and Haemostasis

310

370

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“…In recursive partitioning method analysis, diabetes duration and DNA-histone complex level were significant risk factors of DR. HMWK is not only a marker of kallikrein-kinin system, but also an acute-phase reactant. It might be increased through hepatic synthesis of inflammatory condition in DR. As for factor XIIa, it is considered to be increased during contact system activation of DR [22,28]. The DNAhistone complex level has been reported as a risk factor of DR [6].…”

Section: Discussionmentioning

confidence: 99%

Activation of Factor XII and Kallikrein-Kinin System Combined with Neutrophil Extracellular Trap Formation in Diabetic Retinopathy

Song

Yoo

et al. 2019

Exp Clin Endocrinol Diabetes.

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Background In diabetic retinopathy (DR), neutrophil extracellular traps (NET) and kallikrein-kinin system are considered as contributing factors. However, the detail activation mechanisms has not been fully understood. Since the NET could provide negative-charged surface for factor XII activation and the activated factor XII (XIIa) can initiate kallikrein-kinin system, this study investigated whether patients with DR show activation of NET, factor XII and kallikrein-kinin system. Methods The markers related to NET (DNA-histone complex) and kallikrein-kinin system (high-molecular-weight kininogen, prekallikrein, bradykinin) and factor XIIa were measured in 253 patients with diabetes. To access ex vivo effect of glucose, DNA-histone complex and factor XIIa were measured in whole blood stimulated by glucose. Results The circulating level of DNA-histone complex and factor XIIa were significantly higher in patients with DR than those without DR. In logistic regression analysis, DNA-histone complex, factor XIIa, and high-molecular-weight kininogen were the risk factors of DR. In recursive partitioning analysis, among patients with diabetes duration less than 10 years, patients with high level of DNA-histone complex (>426 AU) showed high risk of DR. In ex vivo experiment, glucose significantly elevated both DNA-histone complex and factor XIIa. Conclusion Our findings suggest that activation of factor XII and kallikrein-kinin system combined with NET formation actively occur in patients with DR and circulating levels of DNA-histone complex, factor XIIa and HMWK can be potential biomarkers to estimate the risk of DR. Strategies against factor XII activation may be beneficial to inhibit DR.

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“…The two chains stay connected with each other by a disulfide bond between Cys340 and Cys367 residues. The heavy chain is responsible for binding to anionic surfaces and, similar to HK heavy chain ( 8 ), links the zymogen to proteoglycans of cell surfaces ( 9 ). The catalytic domain is located within the C-terminal light chain of the protease.…”

Section: Background Of the Plasma Contact Systemmentioning

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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Heparan Sulfate Proteoglycans Mediate Factor XIIa Binding to the Cell Surface

Cited by 23 publications

References 48 publications

The contact activation and kallikrein/kinin systems: pathophysiologic and physiologic activities

The contact activation and kallikrein/kinin systems: pathophysiologic and physiologic activities

Activation of Factor XII and Kallikrein-Kinin System Combined with Neutrophil Extracellular Trap Formation in Diabetic Retinopathy

Factor XII-Driven Inflammatory Reactions with Implications for Anaphylaxis

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