New Aspects in Thrombotic Research: Complement Induced Switch in Mast Cells from a Profibrinolytic to a Prothrombotic Phenotype

Wojta, Johann; Huber, Kurt; Valent, Peter

doi:10.1159/000083842

Cited by 55 publications

(50 citation statements)

References 25 publications

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“…These findings are consistent with the hypothesis put forward by Cho et al [11]. Available data suggest that mast cells play a key role in the regulation of the plasminogen activator/ plasmin system [9]. In a resting state the mast cell is profibrinolytic and antithrombotic representing the only vascular cell type that is able to secrete active t-PA [9].…”

Section: Discussionsupporting

confidence: 89%

“…Available data suggest that mast cells play a key role in the regulation of the plasminogen activator/ plasmin system [9]. In a resting state the mast cell is profibrinolytic and antithrombotic representing the only vascular cell type that is able to secrete active t-PA [9]. In chronic inflammatory diseases with complement activation, including AD, the anaphylotoxin C5a can induce a switch in mast cells to an antifibrinolytic, prothrombotic phenotype that would inhibit fibrinolysis and extracellular proteolysis [9,10].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, in complex with heparin, tryptase might exert anticoagulant properties [8]. On the other hand, mast cells produce tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) [9][10][11]. Additional prothrombotic mechanism could be related to mast cell chymase-mediated rapid proteolysis of tissue factor pathway inhibitor, resulting in reduced anticoagulant activity at the site of inflammation [12].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Plasma fibrin clot properties in atopic dermatitis: links between thrombosis and atopy

Nastałek

Wojas‐Pelc

Undas

2010

J Thromb Thrombolysis

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Myocardial infarction and ischemic stroke are associated with formation of dense fibrin clots resistant to lysis. Although pro- and antithrombotic alterations have been reported in atopy, fibrin clot function has not been studied in atopic patients. The aim of the current study was to investigate fibrin clot properties in patients with atopic dermatitis (AD). Plasma fibrin clot permeability, turbidity and clot lysis were assessed in 130 consecutive AD patients, aged 29.7 +/- 11 [+/-SD] years (mean SCORAD index, 32.4 +/- 14.9), free of thrombotic events. A control group comprised 130 healthy controls matched for demographics. Patients with AD had lower clot permeability (7.12 +/- 1.87 vs. 9.32 +/- 0.86 x 10(-9) cm(2); P < 0.0001), increased fiber thickness (maximum clot absorbancy at 405 nm, 4.03 +/- 0.54 vs. 3.47 +/- 0.25), faster clot formation (the lag phase, 39.16 +/- 4.61 vs. 43.05 +/- 4.56 s), higher maximum D-dimer levels released from clots, reflecting increased clot mass (4.05 +/- 0.57 vs. 3.47 +/- 0.25 mg/l; P < 0.0001), lower rate of D-dimer release (0.073 +/- 0.01 vs. 0.078 +/- 0.01 mg/l/min; P < 0.0001), and prolonged fibrinolysis time (9.26 +/- 1.47 vs. 7.81 +/- 1.17 min; P < 0.0001) compared with controls. Concomitant asthma (n = 36; 27.7%) was related to a higher rate of D-dimer release from clots than the remainder (0.075 +/- 0.01 vs. 0.072 +/- 0.01 mg/l/min, respectively; P = 0.03). Altered plasma fibrin clot properties associated with reduced efficiency of fibrinolysis can be detected in AD patients, which might represent a novel mechanism that modulates a hemostatic balance in atopy.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Plasma fibrin clot properties in atopic dermatitis: links between thrombosis and atopy

Nastałek

Wojas‐Pelc

Undas

2010

J Thromb Thrombolysis

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“…One in vitro study claimed that C5a induces TF activity on endothelial cells (Ikeda et al 1997) and may thereby activate the exogenous coagulation pathway. Recently, a C5a-induced "switch" in mast cells from a pro-fibrinolytic (t-PA release) to a pro-thrombotic phenotype (PAI-1 release) has been reported (Wojta et al 2004) thus modifying the balance between pro-and anticoagulation. To ameliorate the inflammatory response, various immune modulators have been examined, some of which revealed regulatory effects on both the complement and the coagulation system (Weiler and Linhardt 1991;Campbell et al 2001).…”

Section: Interaction Between the Coagulation And Complement Cascade Amentioning

confidence: 99%

Interaction Between the Coagulation and Complement System

Amara

Rittirsch

Flierl

et al. 2008

Advances in Experimental Medicine and Biology

302

282

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The complement system as a main column of innate immunity and the coagulation system as a main column in hemostasis undergo massive activation early after injury. Interactions between the two cascades have often been proposed but the precise molecular pathways of this interplay are still in the dark. To elucidate the mechanisms involved, the effects of various coagulation factors on complement activation and generation of anaphylatoxins were investigated and summarized in the light of the latest literature. Own in vitro findings suggest, that the coagulation factors FXa, FXIa and plasmin may cleave both C5 and C3, and robustly generate C5a and C3a (as detected by immunoblotting and ELISA). The produced anaphylatoxins were found to be biologically active as shown by a dose-dependent chemotactic response of neutrophils and HMC-1 cells, respectively. Thrombin did not only cleave C5 (Huber-Lang et al. 2006) but also in vitro-generated C3a when incubated with native C3. The plasmin-induced cleavage activity could be dose-dependently blocked by the serine protease inhibitor aprotinin and leupeptine. These findings suggest that various serine proteases belonging to the coagulation system are able to activate the complement cascade independently of the established pathways. Moreover, functional C5a and C3a are generated, both of which are known to be crucially involved in the inflammatory response.

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“…TSPO in the cardiovascular system appears to play roles in several aspects of the immune response, such as phagocytosis and the secretion of interleukin-2, interleukin-3, and immunoglobulin A (Veenman & Gavish, 2006). Mast cells are considered to be important for immune response to pathogens (Marshall, 2004) and they have also been implicated in the regulation of thrombosis and inflammation and cardiovascular disease processes such as atherosclerosis as well as in neoplastic conditions (Wojta et al, 2003). Studies have shown that benzodiazepines' inhibition of serotonin release in mast cells could reduce blood brain barrier permeability, influence pain levels, and decrease vascular smooth muscle contractions (Veenman and Gavish, 2006).…”

Section: Involvement Of Tspo In Inflammationmentioning

confidence: 99%

The 18 kDa Translocator Protein and Atherosclerosis in Mice Lacking Apolipoprotein E

Dimitrova-Shumkovska¹,

Veenman²,

Roim³

et al. 2013

Lipid Metabolism

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New Aspects in Thrombotic Research: Complement Induced Switch in Mast Cells from a Profibrinolytic to a Prothrombotic Phenotype

Cited by 55 publications

References 25 publications

Plasma fibrin clot properties in atopic dermatitis: links between thrombosis and atopy

Plasma fibrin clot properties in atopic dermatitis: links between thrombosis and atopy

Interaction Between the Coagulation and Complement System

The 18 kDa Translocator Protein and Atherosclerosis in Mice Lacking Apolipoprotein E

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