scholarly journals Does the conformation of adsorbed fibrinogen dictate platelet interactions with artificial surfaces?

Blood ◽  
1986 ◽  
Vol 68 (2) ◽  
pp. 355-362 ◽  
Author(s):  
JN Lindon ◽  
G McManama ◽  
L Kushner ◽  
EW Merrill ◽  
EW Salzman
Keyword(s):  
Platelet Adhesion ◽  
Surface Coverage ◽  
Platelet Reactivity ◽  
Polymer Surfaces ◽  
Side Chain ◽  
Alkyl Side Chain ◽  
Fibrinogen Binding ◽  
Artificial Surfaces ◽  
Antibody Preparations ◽  
Fibrinogen Adsorption

Abstract Platelet activation by polymer surfaces is thought to require preliminary adsorption of fibrinogen and perhaps changes in fibrinogen conformation. We measured fibrinogen adsorption by a series of polymers by two methods, using either 125I-labeled fibrinogen or 125I-labeled antifibrinogen antibodies, and correlated the results with platelet reactivity (retention and secretion) in columns of beads coated with the polymers. For polyalkyl methacrylates with 1 to 4 carbon side chains, platelet reactivity varied directly with increasing length of the alkyl side chain and with the quantity of bound fibrinogen recognizable by antifibrinogen antibody but not with the total quantity of fibrinogen adsorbed. The same pattern of results was seen with five antibody preparations, including affinity-purified Fab fragments against the D or E domain of fibrinogen. Tests of platelet retention and fibrinogen binding to four polyalkyl acrylates and to three unrelated polymers (polystyrene, polymethyl methacrylate, and a polyether polyurethane) indicated that platelet retention correlated positively with both total fibrinogen binding and with the amount of antibody-recognizable fibrinogen bound. Drugs that block platelet aggregation, but not adhesion, did not alter the hierarchy of platelet retention to the polyalkyl methacrylates. These data suggest that, contrary to previous views, platelet adhesion to artificial surfaces increases with increasing surface coverage of adsorbed fibrinogen if the bound fibrinogen maintains a conformation such that its functional domains remain recognizable by antibody probes.

scholarly journals Does the conformation of adsorbed fibrinogen dictate platelet interactions with artificial surfaces?

Blood ◽  
1986 ◽  
Vol 68 (2) ◽  
pp. 355-362 ◽  
Author(s):  
JN Lindon ◽  
G McManama ◽  
L Kushner ◽  
EW Merrill ◽  
EW Salzman
Keyword(s):  
Platelet Adhesion ◽  
Surface Coverage ◽  
Platelet Reactivity ◽  
Polymer Surfaces ◽  
Side Chain ◽  
Alkyl Side Chain ◽  
Fibrinogen Binding ◽  
Artificial Surfaces ◽  
Antibody Preparations ◽  
Fibrinogen Adsorption

Platelet activation by polymer surfaces is thought to require preliminary adsorption of fibrinogen and perhaps changes in fibrinogen conformation. We measured fibrinogen adsorption by a series of polymers by two methods, using either 125I-labeled fibrinogen or 125I-labeled antifibrinogen antibodies, and correlated the results with platelet reactivity (retention and secretion) in columns of beads coated with the polymers. For polyalkyl methacrylates with 1 to 4 carbon side chains, platelet reactivity varied directly with increasing length of the alkyl side chain and with the quantity of bound fibrinogen recognizable by antifibrinogen antibody but not with the total quantity of fibrinogen adsorbed. The same pattern of results was seen with five antibody preparations, including affinity-purified Fab fragments against the D or E domain of fibrinogen. Tests of platelet retention and fibrinogen binding to four polyalkyl acrylates and to three unrelated polymers (polystyrene, polymethyl methacrylate, and a polyether polyurethane) indicated that platelet retention correlated positively with both total fibrinogen binding and with the amount of antibody-recognizable fibrinogen bound. Drugs that block platelet aggregation, but not adhesion, did not alter the hierarchy of platelet retention to the polyalkyl methacrylates. These data suggest that, contrary to previous views, platelet adhesion to artificial surfaces increases with increasing surface coverage of adsorbed fibrinogen if the bound fibrinogen maintains a conformation such that its functional domains remain recognizable by antibody probes.

DETECTION BY MONOCLONAL ANTIBODIES OF CONFORMATIONAL CHANGE IN FIBRINOGEN ADSORBED ON ARTIFICIAL SURFACES

1987 ◽  
Author(s):  
E Shiba ◽  
J N Lindon ◽  
L Kushner ◽  
B Kudryk ◽  
E W Salzman
Keyword(s):  
Monoclonal Antibodies ◽  
Conformational Change ◽  
Solid Phase ◽  
Platelet Reactivity ◽  
Polyclonal Antibodies ◽  
Total Concentration ◽  
Side Chain ◽  
Alkyl Side Chain ◽  
Artificial Surfaces ◽  
Carbon Side Chain

Adsorption of fibrinogen (Fg) appears to be an important precusor of platelet reactivity with artificial surfaces. We have reported that, contrary to the prevailing view, platelet reactivity is less well correlated with the total concentration of adsorbed Fg on the surface than with the concentration of adsorbed Fg detectable by labelled anti-Fg polyclonal antibodies ("native" Fg), and therefore presumably recognizable by the platelet's Fg receptors. To clarify the nature of the conformational change in Fg implied by these findings, we measured Fg adsorbed on a series of polyalkyl methacrylates, using a solid phase RIA in methacrylate-coated microtiter wells with monoclonal antibodies (MoAb) directed against a variety of Fg epitopes. Total Fg adsorption (125I-Fg) was the same on polymethyl methacrylate (PMMA, single carbon side chain) as on polybutyl methacrylate (PBMA, 4 carbon side chain), but platelet reactivity in a bead column was greater on PBMA than on PMMA. Adsorbed "native" Fg increased with the length of the alkyl side chain when assessed by MoAb against Fg fragment D or E, whole Fg, or γ/γγ chain at the saturated concentration of adsorbed Fg (0.3 ug/cm2) and was significantly greater on PBMA than on PMMA. Adsorbed "native" Fg decreased with length of the alkyl side chain at a lower concentration of Fg (<0.08 ug/cm2) measured with these MoAb. Platelet retention in a polymer bead column was blocked by Fab fragments of these MoAb. These results indicate that Fg molecules adsorbed to some artificial surfaces assume a specfic orientation and conformation that may be important in subsequent interaction of the surface with platelets.

PLATELET ADHESION ON SYNTHETIC SURFACES PRETREATED WITH DILUTED PLASMA IS DETERMINED BY THE SURFACE CONCENTRATION OF "NATIVE" FIBRINOGEN

1987 ◽  
Author(s):  
J N Lindon ◽  
L Kushner ◽  
E Shiba ◽  
E W Salzman
Keyword(s):  
Platelet Activation ◽  
Platelet Adhesion ◽  
Platelet Reactivity ◽  
Surface Concentration ◽  
Native State ◽  
Cooperative Interactions ◽  
Artificial Surfaces ◽  
Flowing Blood ◽  
Native Surface ◽  
Maximum Retention

Platelet adhesion and activation on synthetic surfaces are thought to require the prior adsorption of fibrinogen. We have reported that platelet activation by polyalkyl methacrylates (measured in bead columns exposed to flowing blood) is better correlated with the concentration of conformationally unaltered, "native" (recognizable by radiolabeled antifibrinogen antibodies) bound fibrinogen than with total bound fibrinogen (measured with radiolabeled fibrinogen) following exposure of the surfaces to purified fibrinogen in solution or to diluted blood plasma (Blood 68:355, 1986). We now report that adhesion of washed platelets to polybutyl methacrylate (PBMA; approx. 20% retention in bead columns), was unaffected by preincubation of the surface with whole plasma but was increased significantly by precoating with diluted plasma, with maximum retention (approx. 65%) occurring with plasma diluted 3000-fold. Upon exposure of PBMA to various plasma dilutions the surface concentration of antibody-detectable fibrinogen, but. not of total surface-bound fibrinogen, was correlated with the activation of washed platelets by such pretreated surfaces, With maximal platelet reactivity occurring in columns precoated with the plasma dilution (1:3000) that produced the highest concentration of "native" surface-bound fibrinogen. The plasma dilution that gave maximum total fibrinogen adsorption (100-fold dilution) was not correlated with the concentration of antibody-detectable fibrinogen. Fab fragments of polyclonal anti-fibrinogen antibodies totally prevented platelet activation by PBMA surfaces precoated with diluted plasma. It appears that participation of surface-bound fibrinogen in platelet activation on some artificial surfaces requires that fibrinogen be adsorbed in a conformationally "native" state, presumably thereby permitting multivalent, cooperative interactions with GP IIb/IIIa receptors on platelets.

Further Evidence that Glycoprotein IIb-IIIa Mediates Platelet Spreading on Subendothelium

1991 ◽  
Vol 65 (02) ◽  
pp. 202-205 ◽  
Author(s):  
Harvey J Weiss ◽  
Vincet T Turitto ◽  
Hans R Baumgartner
Keyword(s):  
Platelet Adhesion ◽  
Surface Coverage ◽  
Rabbit Aorta ◽  
Conclusive Evidence ◽  
Initial Contact ◽  
Single Exposure ◽  
Vessel Segment ◽  
Multiple Exposures ◽  
Wall Interaction ◽  
Platelet Spreading

SummaryIn order to explore further the mechanism by which glycoprotein GPIIb-IIIa promotes platelet vessel wall interaction, platelet adhesion to subendothelium was studied in an annular chamber in which subendothelium from rabbit aorta was exposed at a shear rate of 2,600 s−1 to blood from patients with thrombasthenia. Perfusions were conducted for each of 5 exposure times (1 ,2,3, 5 and 10 min), and the percent surface coverage of the vessel segment with platelets in the contact (C) and spread (S) stage was determined. Increased values of platelet contact (C) were obtained in thrombasthenia at all exposure times; this finding is consistent with a defect in platelet spreadirg, based on a previously described kinetic model of platelet attachment to subendothelium. According to this model of attachment, increased values of platelet contact (C) at a single exposure time may be indicative of either a defect in spreading (S) or initial contact (C), but multiple exposures will result in increased contact only for defects which are related to defectiye platelet spreading (s).The results obtained over a broad range of exposure times provide more conclusive evidence that GPIIb-IIIa mediates platelet spreading than those previously obtained at single exposure times.

Baboon Fibrinogen Adsorption and Platelet Adhesion to Polymeric Materials

1991 ◽  
Vol 65 (05) ◽  
pp. 608-617 ◽  
Author(s):  
Joseph A Chinn ◽  
Thomas A Horbett ◽  
Buddy D Ratner
Keyword(s):  
Platelet Adhesion ◽  
Coagulation Factor ◽  
Polymeric Materials ◽  
Platelet Suspension ◽  
Perfusion Chamber ◽  
Static Conditions ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Fibrinogen Adsorption

SummaryThe role of fibrinogen in mediating platelet adhesion to polymers exposed to blood plasma was studied by comparison of the effect of plasma dilution on fibrinogen adsorption and platelet adhesion, and by the use of coagulation factor deficient plasmas. Polyetherurethane substrates were first preadsorbed with dilute plasma, then contacted with washed platelets suspended in a modified, apyrase containing Tyrode’s buffer. Platelet adhesion was studied under static conditions in Multiwell dishes, and also under shearing conditions using a parallel plate perfusion chamber. Fibrinogen adsorption and platelet adhesion were measured using 125I radiolabeled baboon fibrinogen and min radiolabeled baboon platelets, respectively. Surfaces were characterized by electron spectroscopy for chemical analysis (ESCA).When fibrinogen adsorption to Biomer was measured after 2 h contact with a series of dilute plasma solutions under static conditions, a peak in adsorption was observed from 0.26% plasma, i.e., adsorption was greater from 0.26% plasma than from either more or less dilute plasma. A peak in subsequent platelet adhesion to the plasma preadsorbed surfaces, measured after 2 h static incubation with washed platelets, was also observed but occurred on Biomer preadsorbed with 1.0% plasma.When fibrinogen adsorption was measured after 5 min contact under shearing conditions, the fibrinogen adsorption peak occurred on surfaces that had been exposed to 1.0% plasma. A peak in platelet adhesion to these preadsorbed surfaces, measured after 5 min contact with the platelet suspensions under shearing conditions, was observed on Biomer preadsorbed with 0.1% plasma. Shifts between the positions of the peaks in protein adsorption and platelet adhesion occurred on other polymers tested as well.Platelet adhesion was almost completely inhibited when baboon and human plasmas lacking fibrinogen (i. e., serum, heat defibrinogenated plasma, and congenitally afibrinogénémie plasma) were used. Platelet adhesion was restored to near normal when exogenous fibrinogen was added to fibrinogen deficient plasmas. Adhesion was also inhibited completely when a monoclonal antibody directed against the glycoprotein IIb/IIIa complex was added to the platelet suspension. Platelet adhesion to surfaces preadsorbed to von Willebrand factor deficient plasma was the same as to surfaces preadsorbed with normal plasma.While it appears that surface bound fibrinogen does mediate the initial attachment of platelets to Biomer, the observation that the fibrinogen adsorption and platelet adhesion maxima do not coincide exactly also suggests that the degree of subsequent platelet adhesion is dictated not only by the amount of surface bound fibrinogen but also by its conformation.

Platelet Adhesion to Subendothelium - Effect of Shear Rate, Hematocrit and Platelet Count on the Dynamic Equilibrium Between Platelets Adhering to and Detaching from the Surface

1985 ◽  
Vol 54 (04) ◽  
pp. 857-861 ◽  
Author(s):  
Andrea Remuzzi ◽  
Lucia Raffaella Languino ◽  
Vincenzo Costantini ◽  
Vincenzo Guardabasso ◽  
Giovanni de Gartano ◽  
...  
Keyword(s):  
Platelet Adhesion ◽  
Initial Rate ◽  
Dynamic Equilibrium ◽  
Dynamic Condition ◽  
Platelet Reactivity ◽  
Experimental Conditions ◽  
Platelet Suspension ◽  
Shear Rates ◽  
Platelet Concentration ◽  
Adhesion Rate

SummaryThe adherence of human 3H-adenine-labeled platelets to rat subendothelium was quantitated using a rotating probe device. Platelet adhesion increased in relation to the rotation time, reaching a plateau value in about 4-6 min without any further increase. A non-linear fitting analysis of experimental data allowed calculations of initial rate and plateau value of platelet adhesion. Increasing the shear rates (from 35 to 150 sec-1) or the hematocrit (from 10% to 40%), both the adhesion rate and the plateau value were increased. When different platelet concentrations were used the adhesion rate and the plateau calculated increased with platelet concentration. Different plateau values were obtained in the experimental conditions considered. This suggests that the plateau was not reached for the complete occupation of the subendothelial surface by the adherent platelets. Experiments using two different vessels rotated in the same platelet suspension or, viceversa, the same vessel rotated successively in two fresh platelet suspensions, showed that the plateau was not determined by reduced platelet reactivity. Rotating the same vessel first in radiolabeled platelets, until the plateau was reached, and secondly in non labeled platelets, or viceversa, showed that the plateau was indeed a dynamic condition where the number of platelets adhering and detaching reached equilibrium. These observations suggest that the platelet adhesion to subendothelium is the final equilibrium of two platelet fluxes, one adhering to the surface and another detaching from the surface.

The Effect of Heparin vs. Citrate on the Interaction of Platelets with Vascular Graft Materials

1985 ◽  
Vol 54 (04) ◽  
pp. 842-848 ◽  
Author(s):  
Kandice Kottke-Marchant ◽  
James M Anderson ◽  
Albert Rabinovitch ◽  
Richard A Huskey ◽  
Roger Herzig
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Vascular Graft ◽  
Time Course ◽  
Platelet Reactivity ◽  
Polymer Surfaces ◽  
In Vitro Perfusion ◽  
Citrate Anticoagulation ◽  
Platelet Release

SummaryHeparin is known to affect platelet function in vitro, but little is known about the effect of heparin on the interaction of platelets with polymer surfaces in general, and vascular graft materials in particular. For this reason, the effect of heparin vs. citrate anticoagulation on the interaction of platelets with the vascular graft materials expanded polytetrafluoroethylene (ePTFE), Dacron Bionit (DB) and preclotted Dacron Bionit (DB/PC) was studied in a recirculating, in vitro perfusion system. Platelet activation, as shown by a decrease in platelet count, an increase in platelet release and a decrease in platelet aggregation, was observed for all vascular graft materials tested using heparin and was greater for Dacron and preclotted Dacron than for ePTFE. Significant differences between heparin and citrate anticoagulation were seen for platelet release, platelet aggregation and the relative ranking of material platelet-reactivity. However, the trends and time course of platelet activation were similar with both heparin and citrate for the materials tested.

Updated understanding of platelets in thrombosis and hemostasis: the roles of integrin PSI domains and their potential as therapeutic targets

2020 ◽  
Vol 20 ◽  
Author(s):  
Daniel Thomas MacKeigan ◽  
Tiffany Ni ◽  
Chuanbin Shen ◽  
Tyler William Stratton ◽  
Wenjing Ma ◽  
...  
Keyword(s):  
Redox Reactions ◽  
Platelet Adhesion ◽  
Adaptive Mechanism ◽  
Dynamic Interactions ◽  
Surface Receptors ◽  
Isomerase Activity ◽  
Pathological Conditions ◽  
Fibrinogen Binding ◽  
Immune Mediated ◽  
Novel Target

: Platelets are small blood cells known primarily for their ability to adhere and aggregate at injured vessels to arrest bleeding. However, when triggered under pathological conditions, the same adaptive mechanism of platelet adhesion and aggregation may cause thrombosis, a primary cause of heart attack and stroke. Over recent decades, research has made considerable progress in uncovering the intricate and dynamic interactions that regulate these processes. Integrins are heterodimeric cell surface receptors expressed on all metazoan cells that facilitate cell adhesion, movement, and signaling, to drive biological and pathological processes such as thrombosis and hemostasis. Recently, our group discovered that the plexinsemaphorin-integrin (PSI) domains of the integrin β subunits exert endogenous thiol isomerase activity derived from their two highly conserved CXXC active site motifs. Given the importance of redox reactions in integrin activation and its location in the knee region, this PSI domain activity may be critically involved in facilitating the interconversions between integrin conformations. Our monoclonal antibodies against the β3 PSI domain inhibited its thiol isomerase activity and proportionally attenuated fibrinogen binding and platelet aggregation. Notably, these antibodies inhibited thrombosis without significantly impairing hemostasis or causing platelet clearance. In this review, we will update mechanisms of thrombosis and hemostasis including platelet versatilities and immune-mediated thrombocytopenia, discuss critical contributions of the newly discovered PSI domain thiol isomerase activity, and its potential as a novel target for anti-thrombotic therapies and beyond.

An isomerized alkyl side chain enables efficient nonfullerene organic photovoltaics with good tolerance to pre/post-treatments

2021 ◽  
Vol 5 (7) ◽  
pp. 3050-3060 ◽  
Author(s):  
Chenyu Han ◽  
Huanxiang Jiang ◽  
Pengchao Wang ◽  
Lu Yu ◽  
Jianxiao Wang ◽  
...  
Keyword(s):  
Organic Photovoltaics ◽  
Side Chain ◽  
Alkyl Side Chain ◽  
Good Tolerance

An alkyl isomerization strategy is reported to finely modulate the crystallinity of nonfullerene acceptors as well as their photovoltaic responses to post-treatments.

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