[27] Factor XIII (fibrin-stabilizing factor)

Lóránd, L.; Credo, R.B.; Janus, Todd J.

doi:10.1016/s0076-6879(81)80029-8

Cited by 160 publications

(170 citation statements)

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“…Highly purified human plasma-derived FXIIIA2B2 was prepared from the pooled plasma of healthy volunteers and thrombin-activated (FXIIIa) according to the procedure of Lorand et al [19]. In brief, 50 μg/ml (2.4 U/ml) FXIIIA2B2 in 50 mM HEPES, 100 mM NaCl, and 5 mM CaCl2 at pH 7.4 was activated by 20 U/ml human thrombin for 5 min at 37°C; thrombin was then blocked by 30 U/ml hirudin (Sigma-Aldrich, St. Louis, MO).…”

Section: Effect Of Anti-fxiiia Antibodies On Transglutaminase or Pdi mentioning

confidence: 99%

Factor XIII improves platelet adhesion to fibrinogen by protein disulfide isomerase-mediated activity

Lahav

Tvito

Bagoly

et al. 2013

Thrombosis Research

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Background: Factor XIII (FXIII), a plasma pro-transglutaminase, consists of two A subunits and two B subunits (FXIIIA2B2). Following activation by thrombin, it cross-links fibrin chains at the final step of coagulation. We previously reported that FXIII subunit A (FXIIIA) serves as a protein disulfide isomerase (PDI), and that PDI promotes platelet adhesion and aggregation. Objective: This study sought to examine possible mechanistic effect of FXIII on platelet adhesion to fibrinogen; specifically, the role of its PDI activity. Methods: Ex vivo experiments: Blood platelets derived from five patients with hereditary FXIIIA deficiency before and after treatment with Fibrogammin-P (FXIIIA2B2 concentrate) were washed and incubated on immobilized fibrinogen. Bound platelets were stained and counted by microscopy. In vitro experiments: Platelets derived from patients before treatment and five healthy controls were washed and analyzed for adhesion in the presence or absence of Fibrogammin-P or recombinant FXIII (FXIIIA2 concentrate). Results: In ex vivo experiments, one hour after Fibrogammin-P treatment, mean (±SEM) platelet adhesion to fibrinogen increased by 27±2.32% (pb 0.001). In in vitro experiments, treatment with Fibrogammin-P or recombinant FXIII (10 IU/mL each) enhanced platelet adhesion to fibrinogen (in patients, by 29.95±6.7% and 29.05±5.3%, respectively; in controls, by 26.06±3.24% and 26.91±4.72, respectively; pb 0.04 for all). Iodoacetamide-treated FXIII (I-FXIII), where transglutaminase activity is blocked, showed similar enhanced adhesion as untreated FXIII. By contrast, addition of an antibody that specifically blocks FXIIIA-PDI activity inhibited FXIII-mediated platelet adhesion to fibrinogen by 65%. Conclusion: These findings indicate that FXIII-induced enhancement of platelet adhesion is mediated by FXIII-PDI activity.© 2012 Elsevier Ltd. All rights reserved. IntroductionCoagulation factor XIII (FXIII) is a plasma pro-transglutaminase. Following activation by thrombin, it cross-links fibrin chains at the final step of coagulation to form a soluble clot [1]. FXIII circulates in plasma as a heterotetramer of two A subunits (FXIIIA2 -the active transglutaminase) and two B subunits (FXIIIB2 -the carrier protein) [1]. Besides its role in hemostasis, FXIII accelerates wound healing [2], probably by its pro-angiogenic effects [3] as well as by stimulation of monocytes and fibroblasts [4]. Several new lines of evidence point to the involvement of FXIII in platelet function as well [5][6][7][8]. FXIII subunit A (FXIIIA) was detected on thrombin-receptor-activated platelets [5], and platelets were found to adhere to FXIII-covered surface [6]; this interaction depended on the intact fibrinogen binding to integrin αIIbβ3 [5,6]. Accordingly, no clot retraction was noted in FXIIIA knock-out mice [7], and patients with FXIII deficiency, a rare hereditary life-long bleeding disorder [8], showed reduced fibrinogen binding to thrombin-stimulated platelets and reduced platelet adhesion to fibrinogen-covered surface ...

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Section: Effect Of Anti-fxiiia Antibodies On Transglutaminase or Pdi mentioning

confidence: 99%

Factor XIII improves platelet adhesion to fibrinogen by protein disulfide isomerase-mediated activity

Lahav

Tvito

Bagoly

et al. 2013

Thrombosis Research

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“…The persistence of FXIIIa cross-linking activity in clots was examined with various substrates: human 125 I-labeled ␣ 2 AP, 5-(biotinamido)pentylamine, and a peptide, ␣ 2 AP [13][14][15][16][17][18][19][20][21][22][23][24] (in which lysine 24 was biotinylated). Clots were prepared (50 L) in duplicate by combining fibrinogen (2 mg/mL final), CaCl 2 (2 mmol/L final), buffer (Trisbuffered saline, pH 7.4), and thrombin (1 U/mL) and incubating at 37°C.…”

Section: Assays Of Fxiiia Catalytic Life and Substrate Specificitymentioning

confidence: 99%

“…5 Phosphorimages were examined under conditions in which there was a linear relationship between substrate incorporation and pixel volume. In experiments examining the effect of specific amino acid residues on the cross-linking of the ␣ 2 AP [13][14][15][16][17][18][19][20][21][22][23][24] peptide to fibrin, cross-linking was detected by immunoblotting with an anti-peptide antibody directed against this epitope followed by 125 I-labeled protein A and phosphorimaging as described. 13 Plasma clots were formed by mixing 25 L pooled human fresh-frozen plasma (sodium citrate) with 25 L 30 mmol/L CaCl 2 instead of human fibrinogen.…”

Section: Assays Of Fxiiia Catalytic Life and Substrate Specificitymentioning

confidence: 99%

“…After 3 washes, 6 clots were embolized into 2 animals in each of 3 groups: 2 groups had normal clots, and 1 group received clots washed in iodoacetamide (10 mg/mL) and EDTA (10 mmol/L final) to inhibit clot-associated FXIIIa. After embolization, ␣ 2 AP [13][14][15][16][17][18][19][20][21][22][23][24] (final concentration of 0.5 mmol/L) was infused (except in control animals). Four hours after embolization, the ferrets were euthanized by CO 2 inhalation, and the pulmonary emboli were isolated.…”

Section: Cross-linking Of ␣ 2 Ap 13-24 Into Pulmonary Emboli In Vivomentioning

confidence: 99%

“…After 3 washes in PBS, sections were developed in DAB, counterstained in 0.1% methyl green, and mounted. For the detection of ␣ 2 AP [13][14][15][16][17][18][19][20][21][22][23][24] , sections were developed with the ABC reagent and developed as described above.…”

Section: Histologymentioning

confidence: 99%

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Catalytic Life of Activated Factor XIII in Thrombi

2000

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Background-Because the increased fibrinolytic resistance of older thrombi may be caused by the continuous cross-linking action of fibrin-bound activated factor XIII (FXIIIa), we examined the persistence of FXIIIa catalytic activity in clots of various ages. Methods and Results-The time-related changes in FXIIIa activity in clots was measured with (1) ␣ 2 -antiplasmin (␣ 2 AP), a physiological glutamine substrate; (2) ␣ 2 AP 13-24 , a peptide; and (3) pentylamine, a nonspecific lysine substrate. The cross-linking of ␣ 2 AP, ␣ 2 AP 13-24 , and pentylamine into fibrin by clot-bound FXIIIa declined rapidly with half-lives of 19, 21, and 26 minutes, respectively. Mutational studies showed that glutamine 14 (but not glutamine 3 or 16) and valine 17 of ␣ 2 AP 13-24 were required for efficient cross-linking to fibrin. The loss of activity was not due primarily to FXIIIa proteolysis and was partially restored by reducing agents, suggesting that oxidation contributes to the loss of the enzyme's activity in clots. In vivo, the ability of thrombus-bound FXIIIa to cross-link an infused ␣ 2 AP 13-24 peptide into existing pulmonary emboli also declined significantly over time. Conclusions-FXIIIa cross-links ␣ 2 AP and an ␣ 2 AP peptide, in a sequence-specific manner, into formed clots with a catalytic half-life of Ϸ20 minutes. This indicates that FXIIIa activity is a hallmark of new thrombi and that the antifibrinolytic cross-linking effects of FXIIIa are achieved more rapidly in thrombi than previously believed.

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A common mutation in the gene for coagulation factor XIII‐A (VAL34Leu): A risk factor for primary intracerebral hemorrhage is protective against atherothrombotic diseases

et al. 2001

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The role of a common polymorphism in the factor XIII A-subunit gene (FXIII Val34Leu) has been recently investigated as a protective genetic factor against arterial and venous thrombosis. In addition, the less frequent Leu34 allele has been described as a risk factor for intracerebral hemorrhage. We evaluated the prevalence of this polymorphism by PCR in three case-control studies of patients diagnosed as having primary intracerebral hemorrhage (PCH, n = 130), coronary heart diseases (CHD, n = 240; myocardial infarction/no myocardial infarction, 120/120), and cerebrovascular diseases (CVD, n = 240; cerebral infarction/transient ischaemic attack, 120/120). The matched control groups consisted of patients admitted to the hospital without history of vascular disease. In addition, 200 healthy subjects were investigated. The frequency of the mutated allele (Leu34) was higher in patients with PCH than in controls (33.8% vs. 23.1%, P = 0.009) and lower in CHD and CVD patients compared to controls (18.1% vs. 25.2%, P = 0.010 and 17.3% vs. 24.2%, P = 0.011, respectively). Moreover, among the patients with CHD, the Leu34 allele was underrepresented in cases with myocardial infarction than without (12.9% vs. 23.3%, P = 0.004) and than in controls (12.9% vs. 25.2%, P < 0.001). Similar findings were obtained in patients with CVD comparing the cases with cerebral infarction versus cases with transient ischaemic attack (12.5% vs. 22.1%, P = 0.008) and versus controls (12.5% vs. 24.2%, P < 0.001). Finally, considering altogether the groups of ischaemic patients (CHD and CVD, n = 480), it was noted a trend towards a higher mean age of the clinical onset in homozygotes for the Leu allele than in the wild types (P = 0.078). This study indicates that in our population possession of the FXIII Val34Leu mutation predisposes to the occurrence of primary intracerebral hemorrhage and protects against cerebral and myocardial infarction. A wider modulatory role in the progression and onset of atherothrombotic diseases could be ascribed to FXIII Val34Leu. Am.

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[27] Factor XIII (fibrin-stabilizing factor)

Cited by 160 publications

References 9 publications

Factor XIII improves platelet adhesion to fibrinogen by protein disulfide isomerase-mediated activity

Factor XIII improves platelet adhesion to fibrinogen by protein disulfide isomerase-mediated activity

Catalytic Life of Activated Factor XIII in Thrombi

A common mutation in the gene for coagulation factor XIII‐A (VAL34Leu): A risk factor for primary intracerebral hemorrhage is protective against atherothrombotic diseases

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