scholarly journals Mesopore Controls the Responses of Blood Clot‐Immune Complex via Modulating Fibrin Network

2021 ◽  
pp. 2103608
Author(s):  
Shiyu Wu ◽  
Zhengjie Shan ◽  
Lv Xie ◽  
Mengxi Su ◽  
Peisheng Zeng ◽  
...  
Keyword(s):  
Immune Complex ◽  
Blood Clot ◽  
Fibrin Network

scholarly journals Biological Effects of a Root Conditioning Treatment on Periodontally Affected Teeth - An In Vitro Analysis

2016 ◽  
Vol 27 (2) ◽  
pp. 160-168 ◽  
Author(s):  
Aline Cristina Silva ◽  
Camilla Christian Gomes Moura ◽  
Jessica Afonso Ferreira ◽  
Denildo de Magalhães ◽  
Paula Dechichi ◽  
...  
Keyword(s):  
Citric Acid ◽  
Surface Treatment ◽  
Biological Effects ◽  
Blood Clot ◽  
Smear Layer ◽  
Control Group ◽  
Dentin Surface ◽  
Conditioning Treatment ◽  
Fibrin Network

Abstract The aim of this study was to evaluated the root surfaces modifications resulted by application of different chemicals agents, and their influence on the fibrin network and fibroblasts attachment. From 96 anterior mandibular human extracted incisor teeth, 192 dentin blocks of buccal and lingual surface were obtained and randomly divided into 6 groups: Cont- control group, which received no treatment; Root surface scaling and root planing (Srp); Citric acid-Srp; EDTA-Srp; Tetracycline capsule-Srp; Tetracycline gel-Srp. After dentin treatments the specimens were analyzed as follows: 1) demineralization level and residues of the product by scanning electron microscopy (SEM); 2) adhesion of blood components after 20 min of surface treatment by SEM; 3) fibroblast attachment after 24 h by SEM; 4) cell metabolism after 24 h by MTT assay. Data were analyzed using Fisher Exact, One-way ANOVA test followed by Dunn's test, Tukey test and Dunnett test (α=0.05). Citric acid, EDTA and Tetracycline gel resulted in adequate demineralization with no completely smear layer and smear plug removal on root dentin surface. Tetracycline capsule produced great tetracycline residues with several demineralization areas. Tetracycline gel and EDTA groups presented more fibroblast fixation than other experimental groups. The highest mean blood clot adhesion score was observed in roots treated with tetracycline gel. EDTA and Tetracycline gel surface treatment removed the smear layer over dentin surface and promoted adhesion of fibrin network and fibroblast cells attachment.

scholarly journals Nanomechanics of Blood Clot and Thrombus Formation

2022 ◽  
Vol 51 (1) ◽  
Author(s):  
Marco M. Domingues ◽  
Filomena A. Carvalho ◽  
Nuno C. Santos
Keyword(s):  
Mechanical Properties ◽  
Thrombus Formation ◽  
Blood Clot ◽  
Fibrin Clot ◽  
Annual Review ◽  
Publication Date ◽  
New Methods ◽  
Fibrin Network ◽  
Protein Cell

Mechanical properties have been extensively studied in pure elastic or viscous materials; however, most biomaterials possess both physical properties in a viscoelastic component. How the biomechanics of a fibrin clot is related to its composition and the microenvironment where it is formed is not yet fully understood. This review gives an outline of the building mechanisms for blood clot mechanical properties and how they relate to clot function. The formation of a blood clot in health conditions or the formation of a dangerous thrombus go beyond the mere polymerization of fibrinogen into a fibrin network. The complex composition and localization of in vivo fibrin clots demonstrate the interplay between fibrin and/or fibrinogen and blood cells. Studying these protein–cell interactions and clot mechanical properties may represent new methods for the evaluation of cardiovascular diseases (the leading cause of death worldwide), creating new possibilities for clinical diagnosis, prognosis, and therapy. Expected final online publication date for the Annual Review of Biophysics, Volume 51 is May 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Effects of Platelets and Erythrocytes on the Dynamic Size and Mechanical Properties of Blood Clots during Contraction

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4225-4225
Author(s):  
Valerie Tutwiler ◽  
Rustem I. Litvinov ◽  
Tatiana Lebedeva ◽  
Fazoil I. Ataullakhanov ◽  
Douglas B. Cines ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Viscoelastic Properties ◽  
Blood Clot ◽  
Final Size ◽  
Fibrin Network ◽  
Blood Clots ◽  
Platelet Concentration ◽  
Clot Contraction ◽  
Contractile Forces ◽  
Kinetics Of

Abstract Clot contraction is a final step of blood clotting and plays a key role in hemostasis and restoring blood flow past obstructive thrombi. The volume shrinkage of clots is driven by the contractile forces generated by activated platelets and propagated by the platelet-attached viscoelastic fibrin fibers throughout the entire clot. We have recently shown that blood clot contraction results in the formation of compressed. tightly packed, polyhedral erythrocytes (polyhedrocytes) and in the redistribution of platelets and fibrin to the surface of the contracted clot as a result of the complex interplay between platelets, fibrin, and erythrocytes. This study further investigates the role of these major blood cells in the dynamic mechanical (or viscoelastic) properties of the clot and the kinetics of clot contraction. Platelet and erythrocyte levels were varied through the use of partially reconstituted blood. Samples of platelet-containing plasma with or without added erythrocytes were recalcified and activated with thrombin. The viscoelastic properties and the force of contraction of the resultant clot were determined using high precision rheology. The kinetics of contraction was analyzed using a Thromboimager (HemaCore, Moscow, Russia), which allows continuous tracking and quantitative characterization of dynamic clot size by sensing changes in the light scattering of the clot over time. As predicted, the rate and degree of clot contraction depended linearly on the platelet count over a broad range (R2=0.9881). Increased platelet concentration of greater than 500 k/μl resulted in a more than 30% increase (p<0.001) in the percentage of clot contraction at 30 minutes when compared to the lowest platelet concentration (<75 k/μl). There was a significant increase in the rate and a ~15% increase (p<0.001) in the percentage of clot contraction seen in samples with 250-300k/μl, however, and no difference in samples with 125-150k/μl when compared to the lowest platelet concentration. It was observed that increasing the hematocrit level also affected the degree of contraction with a 30% decrease (p<0.001) in the percentage of contraction seen as the erythrocyte level was increased to hematocrit >40% when compared to <10% hematocrit. There was a 10-15% decrease in the percentage of contraction seen at intermediate hematocrit levels (p<0.05). In addition to decreasing the degree of contraction, changing the cellular composition also affected the rate of contraction. Increasing the concentration of either erythrocytes or platelets resulted in a relative increase in the viscous (or plastic) properties when compared to elastic (or stiffness) properties of the clot (p<0.01), showing a complex dependence of the viscoelastic behavior of the contracting clot as a result of the addition of cells. The presence of erythrocytes resulted in a 63% increase (p<0.05) in the contractile forces that were generated by the platelet-fibrin network when compared to platelets alone. We interpret these results as a profound effect of erythrocytes on the course of clot contraction and on the final size and mechanical properties of contracted blood clots. These results reveal that the concentration of cellular components critically affects the ability of the platelet-fibrin network on the outside of the clot to generate forces needed to reduce the clot size and to compact the erythrocytes, resulting in the formation of a stiff, dense hemostatic plug with low permeability. Disclosures Ataullakhanov: HemaCore LLC: Employment, Membership on an entity's Board of Directors or advisory committees.

Fibrin-incorporated vitronectin is involved in platelet adhesion and thrombus formation through homotypic interactions with platelet-associated vitronectin

Blood ◽  
2004 ◽  
Vol 104 (4) ◽  
pp. 1034-1041 ◽  
Author(s):  
Ya-Ping Wu ◽  
Haiko J. Bloemendal ◽  
Emile E. Voest ◽  
Ton Logtenberg ◽  
Philip G. de Groot ◽  
...  
Keyword(s):  
Whole Blood ◽  
Platelet Adhesion ◽  
Surface Coverage ◽  
Thrombus Formation ◽  
Blood Platelets ◽  
Blood Clot ◽  
Human Monoclonal Antibody ◽  
Fold Increase ◽  
Platelet Surface ◽  
Fibrin Network

AbstractWhen a blood clot is formed, vitronectin (VN) is incorporated. Here we studied the consequence of VN incorporation for platelet interactions under flow. Perfusion of whole blood over a fibrin network, formed from purified fibrinogen, resulted in approximately 20% surface coverage with blood platelets. Incorporation of purified multimeric VN into the fibrin network resulted in a 2-fold increase in surface coverage with platelets and in enhancement of platelet aggregate formation. A human monoclonal antibody (huMab VN18), directed against the multimeric form of VN, inhibited platelet adhesion to the combined fibrin/VN matrix to the level of adhesion on fibrin alone. This inhibition was also shown when whole blood was perfused over a plasma-derived clot. Surprisingly, the inhibitory action of the antibody was not directed toward VN incorporated into the fibrin network but toward VN released from the platelets. We conclude that VN-potentiated platelet-clot interaction requires VN in the clot and multimeric VN bound to the platelet surface. Our results provide evidence that homotypic VN interactions contribute to platelet adhesion and aggregation to a blood clot. This report demonstrates for the first time that self-assembly of VN may provide a physiologically relevant contribution to platelet aggregation on a blood clot.

scholarly journals Evaluating the Effects of Fibrinogen αC Mutations on the Ability of Factor XIII to Crosslink the Reactive αC Glutamines (Q237, Q328, Q366)

2019 ◽  
Vol 119 (07) ◽  
pp. 1048-1057
Author(s):  
Kelly Njine Mouapi ◽  
Lucille J. Wagner ◽  
Chad A. Stephens ◽  
Mohammed M. Hindi ◽  
Daniel W. Wilkey ◽  
...  
Keyword(s):  
Factor Xiii ◽  
Blood Clot ◽  
Terminal Segment ◽  
Wild Type ◽  
Binding Region ◽  
Thrombin Cleavage ◽  
Pathological Conditions ◽  
Fibrin Network ◽  
Isopeptide Bonds ◽  
Heteronuclear Single Quantum Correlation

AbstractFibrinogen (Fbg) levels and extent of fibrin polymerization have been associated with various pathological conditions such as cardiovascular disease, arteriosclerosis, and coagulation disorders. Activated factor XIII (FXIIIa) introduces γ-glutamyl-ε-lysinyl isopeptide bonds between reactive glutamines and lysines in the fibrin network to form a blood clot resistant to fibrinolysis. FXIIIa crosslinks the γ-chains and at multiple sites in the αC region of Fbg. Fbg αC contains a FXIII binding site involving αC (389–402) that is located near three glutamines whose reactivities rank Q237 >> Q366 ≈ Q328. Mass spectrometry and two-dimensional heteronuclear single-quantum correlation nuclear magnetic resonance assays were used to probe the anchoring role that αC E396 may play in controlling FXIII function and characterize the effects of Q237 on the reactivities of Q328 and Q366. Studies with αC (233–425) revealed that the E396A mutation does not prevent the transglutaminase function of FXIII A2 or A2B2. Other residues must play a compensatory role in targeting FXIII to αC. Unlike full Fbg, Fbg αC (233–425) did not promote thrombin cleavage of FXIII, an event contributing to activation. With the αC (233–425) E396A mutant, Q237 exhibited slower reactivities compared with αC wild-type (WT) consistent with difficulties in directing this N-terminal segment toward an anchored FXIII interacting at a weaker binding region. Q328 and Q366 became less reactive when Q237 was replaced with inactive N237. Q237 crosslinking is proposed to promote targeting of Q328 and Q366 to the FXIII active site. FXIII thus uses Fbg αC anchoring sites and distinct Q environments to regulate substrate specificity.

scholarly journals The Role of Complement and Platelets in the Dissolution of Thrombin-Induced Clots

1977 ◽  
Author(s):  
Fletcher B. Taylor
Keyword(s):  
Blood Clot ◽  
Fibrin Clot ◽  
Clot Formation ◽  
Clot Lysis ◽  
Temperature Sensitive ◽  
Clot Retraction ◽  
Clinical Value ◽  
Fibrin Network ◽  
Deep Vein

The dilute whole blood clot lysis assay has been used in diagnosis of patients with deep vein thrombophlebitis and pulmonary embolism. Because of its clinical value it has also been the subject of biochemical and physiologic studies of clot lysis of normal diluted blood. This assay reflects the behavior of platelets in that clot lysis as well as clot retraction are platelet dependent. Further, this contribution of platelets is temperature sensitive whereas the rate of fibrin clot formation is not. Thus, this assay offers a convenient model for functional and morphologic studies of temperature induced discontinuity of platelet-fibrin assembly and the interaction of platelet and fibrin in clot formation, retraction and lysis. In these studies the release of serotonin from platelets was correlated with clot formation, retraction, lysis, and clot morphology at 1) 37°, 4° and 4°−37° at 5, 15, 30 and 60 minute intervals. The results suggest that both platelets and fibrinogen are influenced by thrombin used in the assay and that under certain temperature conditions the platelets will release their contents out of phase with the assembly of the fibrin network. In cases where this discontinuity exists, the diluted clots will not retract or lyse normally.

scholarly journals Contribution of Red Blood Cells and Clot Structure to Thrombosis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. SCI-15-SCI-15
Author(s):  
Robert A S Ariens
Keyword(s):  
Atomic Force Microscopy ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Splice Variant ◽  
Blood Clot ◽  
Fibrin Clot ◽  
Force Microscopy ◽  
Atomic Force ◽  
Fibrin Network ◽  
Clot Structure

Abstract The blood clot or thrombus is composed of red blood cells, platelets and white cells that interact with the fibrin meshwork produced by the coagulation system. The red blood cells form polyhedrocytes that seal the clot, platelets provide forces for clot contraction, and white cells contribute neutrophil extracellular traps, cytokines and complement activation. The fibrin network contributes clot elasticity and provides the proteinaceous backbone structure that stabilises the clot. Previous studies from our laboratory and others have shown that dense fibrin networks demonstrating small pores and increased resistance to fibrinolysis associate with thrombosis. However, the mechanisms underpinning this have not been fully understood. Recent studies using atomic force microscopy from our laboratory have shown that fibrinogen interacts with red cells with comparable affinity as that with platelets. A patient with mutations in the β3 integrin subunit showed no binding between red cells and fibrinogen, demonstrating that a β3-related integrin receptor is involved in the interaction. Mutations in the fibrinogen α-chain integrin binding sites (D97E and D574E) reduced frequency of red cell interactions with fibrinogen. Interestingly, a naturally occuring splice variant of the fibrinogen γ-chain that reduces binding to the platelets, fibrinogen γ', increased binding interactions between fibrinogen and red blood cells. Fibrinogen γ' is a naturally occurring splice variant of fibrinogen, in which the C-terminal AGDV residues of the more common γA-chain (85%) are replaced with a negatively charched VRPEHPAETEYDSLYPEDDL sequence of the γ' chain (15%). Fibrinogen γ' induced clustering of fibrin fibres into tightly interknit nuclei of fibrin fibres, interspersed by large pores that extend over more than 50 μm within the fibrin network structure. The effects of fibrinogen γ' on fibrin clot structure was independent of thrombin and FXIII as demonstrated using snake venom enzyme. Previously we showed impaired fibrin protofibril formation with fibrinogen γ' using atomic force microscopy. Using turbidimetric analysis of fibrin intrafibrillar structure, we show that fibrinogen γ' reduces protofibil packing per fibrin fiber. Furthermore, we find that reduced protofibril packing diminishes fibrin stiffness as analysed with magnetic tweezers both in purified systems as well as in plasma at (patho)physiological fibrinogen γ' levels that range from 3-40%, and in whole blood as analysed with thromboelastography. In conclusion, our data show that red blood cells and fibrinogen γ' play major roles in the regulation of clot structure and stability, and that these effects on clot structure are major determinants of the functional properties of the blood clot. Modulating fibrin clot structure and its interactions with blood cells may represent major new targets for the treatment of thrombosis. Disclosures No relevant conflicts of interest to declare.

scholarly journals An implantable blood clot–based immune niche for enhanced cancer vaccination

2020 ◽  
Vol 6 (39) ◽  
pp. eabb4639 ◽  
Author(s):  
Qin Fan ◽  
Qingle Ma ◽  
Jingyu Bai ◽  
Jialu Xu ◽  
Ziying Fei ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
Ex Vivo ◽  
Blood Clot ◽  
Autologous Blood ◽  
Immune Checkpoint Blockade ◽  
Cancer Vaccination ◽  
Patients With Cancer ◽  
Tumor Associated Antigen ◽  
Fibrin Network ◽  
Personalized Cancer

Cancer immunotherapy using cancer vaccines has shown great potential in the prevention and treatment of cancer. Here, we report an implantable autologous blood clot scaffold for enhanced cancer vaccination. It comprises a gel-like fibrin network formed by coagulation of blood to trap a large number of red blood cells. Upon implantation, the cross-linked RBCs in the blood clot can attract and recruit a great number of immune cells, leading to the formation of an “immune niche.” Encapsulated with tumor-associated antigen and adjuvant, the blood clot vaccine (BCV) can induce a robust anticancer immune response. The BCV combined with immune checkpoint blockade effectively inhibits tumor growth in B16F10 and 4T1 tumor models. The proposed implantable blood clot cancer vaccine can be readily made by mixing the blood from patients with cancer with immunomodulating agents ex vivo, followed by reimplantation into the same patient for personalized cancer immunotherapy in future clinical translation.

Experimental Amyloidosis Induced by Immune Complex

1971 ◽  
Vol 29 ◽  
pp. 582-583
Author(s):  
A. Kawaoi
Keyword(s):  
Immune Complex ◽  
Systemic Amyloidosis ◽  
Human Diseases ◽  
Experimental Amyloidosis ◽  
Freund’S Complete Adjuvant ◽  
Freund's Complete Adjuvant ◽  
Immunological Approach ◽  
Experimentally Induced

Numbers of immunological approach have been made to the amyloidosis through the variety of predisposing human diseases and the experimentally induced animals by the greater number of agents. The results suggest an important role of impaired immunity involving both humoral and cell-mediated aspects.Recently the author has succeeded in producing amyloidosis in the rabbits and mice by the injections of immune complex of heat denatured DNA.The aim of this report is to demonstrate the details of the ultrastructure of the amyloidosis induced by heterologous insoluble immune complex. Eleven of twelve mice, dd strain, subcutaneously injected twice a week with Freund's complete adjuvant and four of seven animals intraperitonially injected developed systemic amyloidosis two months later from the initial injections. The spleens were electron microscopically observed.

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