Abnormal Wound Healing in Experimentally-Induced Factor XIII Deficiency in Rabbits

1979 ◽  
Author(s):  
Soo Young Lee ◽  
S. I. Chung
Keyword(s):  
Wound Healing ◽  
Factor Xiii ◽  
Tissue Repair ◽  
Culture Media ◽  
Rabbit Platelet ◽  
Fibroblast Proliferation ◽  
Factor Xiii Deficiency ◽  
Platelet Factor ◽  
Collagenous Matrix ◽  
Matrix Accumulation

The observation of poor wound healing and abnormal scarring in Factor XIII deficiency reported by Duekert et al., (Throab. Diath. Haenorrh., 5:179, 1960) aroused great interest in the role of this factor in tissue repair. In the present atudy, Factor XIII deficiency was induced in rabbits by intravenous infusion of IgC isolated from goat anti-rabbit platelet Factor XIII, and the deficient state vaa maintained by daily infusion. Control rabbits were given normal goat IgG. After production of standard akin wound the progress of eptthellalizacion, fibroblast proliferation, and collagenous matrix formation was monitored by histology and immunohiscocherais try. In normal rabbits, epithelialization was complete by day 6; fibroblast proliferation by day 10; maximal collagenous matrix accumulation was observed on day 14. In Factor XIII deficient animals, epithelialixation was not completed until day 14; fibroblast proliferation and collagenous matrix accumulation were retarded beyond day 20. These observations suggest that Factor XIII is involved in early phases of wound healing. In an initial attempt to study the mode of Factor XIII in tissue repair, the effect of Factor XIII ou the growth of fibroblast was examined in vitro. However, contrary to an earlier report, the addition of Factor XIII to the culture media shoved no effect on the growth of cells.

Prevention Of Shwartzman’S Phenomenon In Factor XIII Deficiency

1981 ◽  
Author(s):  
Soo Young Lee ◽  
Sung Keun Chang ◽  
Soo II Chung
Keyword(s):  
Factor Xiii ◽  
Rabbit Platelet ◽  
Factor Xiii Deficiency ◽  
Platelet Factor ◽  
Cortical Necrosis ◽  
Rate Of Increase ◽  
Shwartzman Reaction

Cross-linked clots formed in vitro are reported to be more resistant to fibrinolysis but the relevance of these observations to the situation in vivo is uncertain. The possible role of Factor XIII in the formation of diffuse intravascular fibrin deposition was examined in experimentally induced Factor XIII deficient rabbits. Factor XIII deficiency was induced by intravenous infusion of IgG isolated from goat anti-rabbit platelet Factor XIII. Control received normal goat IgG. The Shwartzman reaction was produced by two injections of bacterial endotoxin given 24 hours apart.The most striking histological differences were observed after 48 hours. A large number of glomerular loops were enlarged and engorged with red blood cells and platelet- fibrin thrombi; extensive bilateral cortical necrosis was observed in 8 out of 10 endotoxin injected control rabbits but none in the Factor XIII deficient group.Fibrinogen levels in control rabbits were increased 3-4 fold (1.1g/100 ml), at 24 hours and slightly decreased at 48 hours after endotoxin injection, whereas in Factor XIII deficient animals, the rate of increase was slower but reached similar levels at 48 hours. Fibrinolytic activity in vivo, studied by the degradation of infused 125I-fibrinogen, was significantly increased in both endotoxin injected groups, irrespective of Factor XIII levels.These results strongly suggest that cross-linked thrombi are more resistant to fibrinolysis in vivo as well as in vitro.

scholarly journals Factor XIII Deficiency Causes Cardiac Rupture, Impairs Wound Healing, and Aggravates Cardiac Remodeling in Mice With Myocardial Infarction

Circulation ◽  
2006 ◽  
Vol 113 (9) ◽  
pp. 1196-1202 ◽  
Author(s):  
Matthias Nahrendorf ◽  
Kai Hu ◽  
Stefan Frantz ◽  
Farouc A. Jaffer ◽  
Ching-Hsuan Tung ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Wound Healing ◽  
Cardiac Remodeling ◽  
Factor Xiii ◽  
Cardiac Rupture ◽  
Factor Xiii Deficiency

Substrates of Factor XIII-A: roles in thrombosis and wound healing

2012 ◽  
Vol 124 (3) ◽  
pp. 123-137 ◽  
Author(s):  
Victoria R. Richardson ◽  
Paul Cordell ◽  
Kristina F. Standeven ◽  
Angela M. Carter
Keyword(s):  
Wound Healing ◽  
Factor Xiii ◽  
Tissue Repair ◽  
Cross Linking ◽  
Clot Retraction ◽  
Matrix Deposition ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Cell Matrix Interactions

FXIII (Factor XIII) is a Ca2+-dependent enzyme which forms covalent ϵ-(γ-glutamyl)lysine cross-links between the γ-carboxy-amine group of a glutamine residue and the ϵ-amino group of a lysine residue. FXIII was originally identified as a protein involved in fibrin clot stabilization; however, additional extracellular and intracellular roles for FXIII have been identified which influence thrombus resolution and tissue repair. The present review discusses the substrates of FXIIIa (activated FXIII) involved in thrombosis and wound healing with a particular focus on: (i) the influence of plasma FXIIIa on the formation of stable fibrin clots able to withstand mechanical and enzymatic breakdown through fibrin–fibrin cross-linking and cross-linking of fibrinolysis inhibitors, in particular α2-antiplasmin; (ii) the role of intracellular FXIIIa in clot retraction through cross-linking of platelet cytoskeleton proteins, including actin, myosin, filamin and vinculin; (iii) the role of intracellular FXIIIa in cross-linking the cytoplasmic tails of monocyte AT1Rs (angiotensin type 1 receptors) and potential effects on the development of atherosclerosis; and (iv) the role of FXIIIa on matrix deposition and tissue repair, including cross-linking of extracellular matrix proteins, such as fibronectin, collagen and von Willebrand factor, and the effects on matrix deposition and cell–matrix interactions. The review highlights the central role of FXIIIa in the regulation of thrombus stability, thrombus regulation, cell–matrix interactions and wound healing, which is supported by observations in FXIII-deficient humans and animals.

scholarly journals Coagulation factor XIII: a multifunctional transglutaminase with clinical potential in a range of conditions

2015 ◽  
Vol 113 (04) ◽  
pp. 686-697 ◽  
Author(s):  
Heiko Herwald ◽  
Wolfgang Korte ◽  
Yannick Allanore ◽  
Christopher P. Denton ◽  
Marco Matucci Cerinic ◽  
...  
Keyword(s):  
Wound Healing ◽  
Factor Xiii ◽  
Tissue Repair ◽  
Coagulation Factor ◽  
Coagulation Cascade ◽  
Cross Linking ◽  
Principal Mechanism ◽  
Coagulation Factor Xiii ◽  
Perioperative Bleeding ◽  
Wide Range

SummaryCoagulation factor XIII (FXIII), a plasma transglutaminase, is best known as the final enzyme in the coagulation cascade, where it is responsible for cross-linking of fibrin. However, a growing body of evidence has demonstrated that FXIII targets a wide range of additional substrates that have important roles in health and disease. These include antifibrinolytic proteins, with cross-linking of α2-antiplasmin to fibrin, and potentially fibrinogen, being the principal mechanism(s) whereby plasmin-mediated clot degradation is minimised. FXIII also acts on endothelial cell VEGFR-2 and α2β3 integrin, which ultimately leads to downregulation of the antiangiogenic protein thrombospondin-1, promoting angiogenesis and neovascularisation. Under infectious disease conditions, FXIII cross-links bacterial surface proteins to fibrinogen, resulting in immobilisation and killing, while during wound healing, FXIII induces cross-linking of the provisional matrix. The latter process has been shown to influence the interaction of leukocytes with the provisional extracellular matrix and promote wound healing. Through these actions, there are good rationales for evaluating the therapeutic potential of FXIII in diseases in which tissue repair is dysregulated or perturbed, including systemic sclerosis (scleroderma), invasive bacterial infections, and tissue repair, for instance healing of venous leg ulcers or myocardial injuries. Adequate levels of FXIII are also required in patients undergoing surgery to prevent or treat perioperative bleeding, and its augmentation in patients with/at risk for perioperative bleeding may also have potential clinical benefit. While there are preclinical and/or clinical data to support the use of FXIII in a range of settings, further clinical evaluation in these underexplored applications is warranted.

Factor XIII Associates with the Guanine Exchange Factors Cool-1 and Cool-2 in Human Platelets.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4015-4015
Author(s):  
Alex Morgan-Spencer ◽  
Daniel L. Greenberg
Keyword(s):  
Factor Xiii ◽  
Conflicts Of Interest ◽  
Focal Adhesions ◽  
Human Platelets ◽  
Cytoskeletal Proteins ◽  
Factor Xiii Deficiency ◽  
Platelet Factor ◽  
Platelet Surface ◽  
Loaded State ◽  
Guanine Exchange Factors

Abstract Abstract 4015 Poster Board III-951 A major signaling pathway that regulates platelet shape change and reorganization of the cytoskeleton involves the Rho family of GTPases; CDC42, Rac1 and RhoA. These GTPases are converted from their inactive or GDP-loaded state to the active or GTP-loaded state by a class of enzymes called Guanine Exchange Factors (GEFs). GEFs are a family of multi-domain proteins that contain a GDP-GTP exchange domain (DH-PH) as well as other protein interacting domains that are regulated by the activation of receptors present on the platelet surface. We previously identified the presence of two homologous GEFs, Cool-1 and Cool-2, in human platelets. In nucleated cells, the activities and substrate specificities of the Cool GEFs are regulated by complex interactions with p21-activated kinases (PAK), Gb/g heterodimers, focal adhesion kinase, and the scaffolding proteins GIT-1 and GIT-2. The Cool GEFs are found at the sites of focal adhesions during spreading and migration in nucleated cells, however, little is known about the regulation or activity of Cool-1 or Cool-2 in platelets. Co-immunoprecipitation experiments were performed with Cool-1 and Cool-2 antibodies using lysates from resting and thrombin stimulated human platelets. We analyzed the precipitated proteins by Mass Spectroscopy and found a number of structural and scaffold proteins bound to the Cool GEFs in the thrombin activated lysates. These cytoskeletal proteins include talin, multimerin, tubulin, filamin A, actin and fibrinogen. Interestingly, a large number of Factor XIII also co-immunoprecipitated with Cool-1 and Cool-2 in the thrombin activated platelet lysates. Western analysis of the co-immunoprecipated platelet proteins from thrombin, TRAP1 and TRAP4 demonstrated that the association of factor XIII with the Cool GEFs is calcium dependent. Inhibition of transglutaminase activity and presence of RGD peptide did not affect the association of Factor XIII with Cool-1 or Cool-2. Factor XIII deficiency is commonly thought to result in bleeding due to the impaired crosslinking of fibrin. However, platelet factor XIII may also play an important role in cross linking platelet cytoskeleletal proteins such as actin and myosin. Consistent with that hypothesis is a recent report showing that platelet factor XIII deficiency results in decreased lamellapodia formation under static adhesive conditions. The association of Factor XIII with the Cool GEFs further supports investigating the potential for the transglutaminase to crosslink platelet cytoskeletal proteins. Disclosures: No relevant conflicts of interest to declare.

Bleeding Disorder with Abnormal Wound Healing, Acid-Soluble Clots and Normal Factor XIII

1976 ◽  
Vol 36 (03) ◽  
pp. 537-541 ◽  
Author(s):  
Stefan Ragaz ◽  
Graham Kemp ◽  
Miha Furlan ◽  
Eugene A. Beck
Keyword(s):  
Wound Healing ◽  
Factor Xiii ◽  
Low Ph ◽  
Bleeding Disorder ◽  
Red Cell ◽  
Factor Xiii Deficiency ◽  
Plasma Clot ◽  
Massive Blood Transfusion ◽  
Solubility Test ◽  
Sustained Increase

SummaryAn unusual bleeding disorder clinically resembling factor XIII deficiency is presented. The only detectable coagulation abnormality was rapid clot dissolution in 1% monochloroacetic acid. This abnormality was ascribed to the sustained increase of a pepsin-like plasma protease which is activated at low pH. A systematic search for similar phenomena revealed that massive blood transfusion may also enhance plasma-clot solubility in acid, possibly by release of a red cell protease. We conclude that the acid clot solubility test is not a specific indicator of factor XIII deficiency, but this simple assay is recommended for further studies of acid plasma protease activity. The diagnostic relevance and pathophysiologic importance of increased pepsin-like activity in plasma remain to be elucidated.

New Families with Hereditary Hemorrhagic Trait due to Deficiency of Fibrin Stabilizing Factor (F. XIII)

1968 ◽  
Vol 20 (03/04) ◽  
pp. 534-541 ◽  
Author(s):  
O Egeberg
Keyword(s):  
Factor Xiii ◽  
Family Members ◽  
Recessive Inheritance ◽  
Factor Xiii Deficiency ◽  
History Of ◽  
Congenital Factor

SummarySevere hemorrhagic disorder due to congenital factor XIII deficiency is described in two unrelated Norwegian girls.Plasma cephalin time was for both patients extraordinarily short during episodes of bleeding and hematomas. No such hyperactivity reaction was demonstrable in unaffected condition some months later.Estimations of blood factor XIII levels revealed a partial defect in the parents of both children, and also in some other family members, consistent with an autosomal incompletely recessive inheritance of the defect. Some of the presumptive heterozygotes had a history of light bleeding phenomenons; whether this was related to their partial lack of factor XIII is so far uncertain.

Plasma Factor XIII and Platelet Factor XIII in Hyperlipaemia

1976 ◽  
Vol 36 (03) ◽  
pp. 542-550 ◽  
Author(s):  
Mircea P. Cucuianu ◽  
K Miloszewski ◽  
D Porutiu ◽  
M. S Losowsky
Keyword(s):  
Factor Xiii ◽  
Significant Contribution ◽  
Quantitative Assay ◽  
Factor Xii ◽  
Platelet Factor ◽  
Type Iv ◽  
Plasma Factor ◽  
Hepatic Synthesis

SummaryPlasma factor XIII activity measured by a quantitative assay was found to be significantly higher in hypertriglyceridaemic patients (type IV and combined hyperlipoproteinaemia), as compared to normolipaemic controls. No such elevation in plasma factor XIII activity was found in patients with type IIa hyperlipaemia. Plasma pseudocholinesterase was found to parallel the elevated factor XIII activity in hypertriglyceridaemic subjects.In contrast, platelet factor XIII activity was not raised in hyperlipaemic subjects, and plasma factor XIII was found to be normal in a normolipaemic subject with throm-bocythaemia.It was concluded that there is no significant contribution from platelets to plasma factor XIII activity, and that the observed increase in plasma factor XII in hypertriglyceridaemia results from enhanced hepatic synthesis of the enzyme.

Determination of Factor XIII Activity and of Factor XIII Inhibitors Using an Ammonium-Sensitive Electrode

1983 ◽  
Vol 50 (02) ◽  
pp. 563-566 ◽  
Author(s):  
P Hellstern ◽  
K Schilz ◽  
G von Blohn ◽  
E Wenzel
Keyword(s):  
Factor Xiii ◽  
Normal Subjects ◽  
The Other ◽  
Activity Measurement ◽  
Factor Xiii Deficiency ◽  
Assay Procedure ◽  
Stabilization Factor ◽  
Release Method ◽  
Sensitive Electrode

SummaryAn assay for rapid factor XIII activity measurement has been developed based on the determination of the ammonium released during fibrin stabilization. Factor XIII was activated by thrombin and calcium. Ammonium was measured by an ammonium-sensitive electrode. It was demonstrated that the assay procedure yields accurate and precise results and that factor XIII-catalyzed fibrin stabilization can be measured kinetically. The amount of ammonium released during the first 90 min of fibrin stabilization was found to be 7.8 ± 0.5 moles per mole fibrinogen, which is in agreement with the findings of other authors. In 15 normal subjects and in 15 patients suffering from diseases with suspected factor XIII deficiency there was a satisfactory correlation between the results obtained by the “ammonium-release-method”, Bohn’s method, and the immunological assay (r1 = 0.65; r2= 0.70; p<0.01). In 3 of 5 patients with paraproteinemias the values of factor XIII activity determined by the ammonium-release method were markedly lower than those estimated by the other methods. It could be shown that inhibitor mechanisms were responsible for these discrepancies.

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