Determination of the cut-off score of Human platelets membrane glycoprotein IIb/IIIa in COVID19: A novel biomarker and a therapeutic target

2021 ◽  
Vol 0 (0) ◽  
pp. 0-0
Author(s):  
Hewida Fadel ◽  
Mohamed Ahmed ◽  
Mohammed Mohamed ◽  
Reda Almiry
Keyword(s):  
Therapeutic Target ◽  
Human Platelets ◽  
Membrane Glycoprotein

Differential Ability of Agonists to Express Distinct Pools of Fibrinogen (Gpllb/llla) Receptors which Can Mediate the Aggregation of Human Platelets

1989 ◽  
Vol 62 (03) ◽  
pp. 955-961 ◽  
Author(s):  
Ian S Watts ◽  
Rebecca J Keery ◽  
Philip Lumley
Keyword(s):  
Platelet Aggregation ◽  
Human Platelet ◽  
Surface Membrane ◽  
Blood Platelet ◽  
Human Platelets ◽  
Membrane Glycoprotein ◽  
Platelet Surface ◽  
Human Platelet Aggregation ◽  
Differential Ability ◽  
Blood Platelet Aggregation

SummaryWe have investigated the effect of two procedures that modify human platelet surface membrane glycoprotein (Gp) IIb and IIIa complexes upon whole blood platelet aggregation to a range of agonists. (A) Irreversible disruption of complexes by temporary (30 min) Ca2+-deprivation with EGTA at 37° C. (B) Binding of a monoclonal antibody M148 to the complex. EGTA exposure abolished aggregation to ADP, adrenaline and PAF. In contrast, full aggregation curves to collagen and U-46619 could still be established. EGTA exposure reduced M148 binding to platelets by 80%. Excess M148 abolished aggregation to ADP, PAF, collagen and U-46619. However, upon removal of unbound antibody from platelets full aggregation curves to collagen and U-46619 but not to ADP and PAF could be re-established. Thus human platelet aggregation to ADP, PAF and adrenaline appears absolutely dependent upon surface membrane GpIIb/IIIa complexes. In contrast, collagen and U-46619 cause expression of an additional distinct pool of Gp complexes inaccessible to EGTA and M148 in unstimulated platelets which is intimately involved in aggregation to these agonists.

Galactosyltransferase and membrane glycoprotein abnormality in human platelets from Tn-syndrome donors

Nature ◽  
1979 ◽  
Vol 282 (5739) ◽  
pp. 621-623 ◽  
Author(s):  
J. P. Cartron ◽  
A. T. Nurden
Keyword(s):  
Human Platelets ◽  
Membrane Glycoprotein

scholarly journals Identification of the first small-molecule ligand of the neuronal receptor sortilin and structure determination of the receptor–ligand complex

2014 ◽  
Vol 70 (2) ◽  
pp. 451-460 ◽  
Author(s):  
Jacob Lauwring Andersen ◽  
Tenna Juul Schrøder ◽  
Søren Christensen ◽  
Dorthe Strandbygård ◽  
Lone Tjener Pallesen ◽  
...  
Keyword(s):  
Small Molecule ◽  
Binding Mode ◽  
Membrane Glycoprotein ◽  
Type I ◽  
Ligand Complex ◽  
Neuronal Viability ◽  
The Central Nervous System ◽  
Vacuolar Protein ◽  
Small Molecule Ligand

Sortilin is a type I membrane glycoprotein belonging to the vacuolar protein sorting 10 protein (Vps10p) family of sorting receptors and is most abundantly expressed in the central nervous system. Sortilin has emerged as a key player in the regulation of neuronal viability and has been implicated as a possible therapeutic target in a range of disorders. Here, the identification of AF40431, the first reported small-molecule ligand of sortilin, is reported. Crystals of the sortilin–AF40431 complex were obtained by co-crystallization and the structure of the complex was solved to 2.7 Å resolution. AF40431 is bound in the neurotensin-binding site of sortilin, with the leucine moiety of AF40431 mimicking the binding mode of the C-terminal leucine of neurotensin and the 4-methylumbelliferone moiety of AF40431 forming π-stacking with a phenylalanine.

The Use of Monoclonal Antibodies to Human Platelet Membrane Glycoprotein IIb-IIIa to Quantitate Platelet Deposition on Artificial Surfaces

1987 ◽  
Vol 58 (02) ◽  
pp. 724-731 ◽  
Author(s):  
Juliette N Mulvihill ◽  
Han G Huisman ◽  
Jean-Pierre Cazenave ◽  
Jan A van Mourik ◽  
Willem G van Aken
Keyword(s):  
Whole Blood ◽  
Human Albumin ◽  
Human Platelets ◽  
Membrane Glycoprotein ◽  
Bovine Collagen ◽  
Glass Capillaries ◽  
Platelet Deposition ◽  
A New Technique ◽  
Albumin Adsorption

SummaryA new technique is described to quantitate platelet deposition in vitro on artifical surfaces, based on a surface phase radioimmunoassay using the monoclonal antibody 6C9, directed specifically against the membrane glycoprotein complex IIb-IIIa of human platelets. Results correlate in linear fashion with those obtained using 111Indium labeled platelets. The method offers particular advantages for the measurement of platelet deposition in whole blood, since platelet separation, washing and labeling procedures are eliminated, together with the ensuing possible selection of platelet populations. In vitro perfusion is performed in glass capillaries of precisely defined diameter (0.80 or 0.56 mm i.d.). Blood flow is laminar and accurately controlled over wall shear rates ranging from venous to capillary (50-4,000 s-1). Using glass capillaries precoated with purified human albumin or fibrinogen or bovine collagen, platelet deposition from suspensions of washed human platelets in Tyrode's-albumin buffer in the presence of a 40% hematocrit is (platelets/mm2): 11,000 (albumin), 78,000 (fibrinogen) and 306,000 (collagen) after 5 min perfusion at 2,000 s-1. In heparin, citrate or hirudin anticoagulated whole blood, surfaces are passivated, probably by albumin adsorption from plasma (platelets/mm2): 400 (albumin), 3,600 (fibrinogen) and 48,000 (collagen) after 5 min perfusion in the presence of 13 mM citrate.

Determination of the Density Distribution of Human Platelets - Methodological Aspects and Comparison with Other Tests for Platelet Activation

1982 ◽  
Vol 47 (03) ◽  
pp. 239-243 ◽  
Author(s):  
B A van Oost ◽  
I H van Hien-Hagg ◽  
B F E Veldhuyzen ◽  
A P M Timmermans ◽  
J J Sixma
Keyword(s):  
Platelet Activation ◽  
Gradient Centrifugation ◽  
Buoyant Density ◽  
Human Platelets ◽  
Thrombotic Disease ◽  
Platelet Aggregate ◽  
Thrombotic Complications ◽  
Methodological Aspects ◽  
Function Testing

SummaryStimulation of human platelets to release results in decreased buoyant density. This decreased density provides a tool to detect circulating platelets which have participated in a thrombotic process. Platelet density gradient centrifugation using Stractan was standardized and the effects of anticoagulation, temperature, and osmolarity were investigated. In 7 out of 32 patients with thrombotic disease less dense platelets were found. Platelet activation in the patient group was also indicated by spontaneous aggregation (10/32), decreased circulating platelet aggregate ratios (5/24) and elevated plasma β-thromboglobulin levels (2/11). Several of these tests were also abnormal in diabetes mellitus thrombocytosis, leukaemia and several systemic diseases with thrombotic complications. The platelet density test using Stractan is reproducible and independent of other tests for platelet activation and is therefore potentially a useful extension of platelet function testing in patients with thrombotic disease.

Absence of the 145,000 Molecular Weight, Soluble Platelet Membrane Glycoprotein - Lack of Platelet Agglutination

1979 ◽  
Vol 42 (05) ◽  
pp. 1626-1629 ◽  
Author(s):  
Nils Olav Solum ◽  
Inger Hagen ◽  
Miroslav Peterka ◽  
Torbjørn Gjemdal
Keyword(s):  
Molecular Weight ◽  
Factor Viii ◽  
Human Platelets ◽  
Platelet Membrane ◽  
Membrane Glycoprotein ◽  
Related Protein ◽  
Giant Platelets ◽  
Platelet Membrane Glycoprotein ◽  
Human Factor Viii ◽  
Bovine Factor

SummaryOne step in the function of platelets in hemostasis is their adhesion to subendothelial tissue. The human factor VIII related protein (von Willebrand factor) is considered to be involved in the adhesion phenomenon (Baumgartner et al. 1977). One manifestation of the protein-cell interaction can be observed as a platelet agglutination after addition to the human platelets of a combination of the human protein and the glycopeptide ristocetin, or after addition of the bovine protein alone. The bovine factor VIII related protein as such directly binds to the platelet membrane (Kirby and Sha May Tang 1977) and thus represents a simpler system than ristocetin plus the human cofactor which may have to interact with each other before excerting their effect on the platelet membrane. The present paper concerns the se.One of the characteristics of the agglutination of human platelets brought about by the bovine factor VIII related protein (as well as by ristocetin plus the human cofactor) is that it is independent of the energy metabolism and the internal organization of the platelet. One would therefore expect that modified platelets and platelet “ghosts” would agglutinate as long as certain structures on the outer cell surface are chemically and sterically intact. Because of the hydrophilic character of the carbohydrate side chains, the membrane glycoproteins are considered of special importance for cell contact phenomena. Thus it has already been known for some years that giant platelets of the Bernard-Soulier type which do not agglutinate with the bovine protein (Bithell et al. 1972), contain a reduced amount of sialic acid related to protein content and surface area (Grottum and Solum 1969), and show a reduced glycoprotein stain in the GP I region on SDS polyacrylamide gel electrophoresis (Nurden and Caen 1975).This paper presents five observations which support a working hypothesis stating that the presence on the platelet membrane of the 145,000 molecular weight, soluble platelet membrane glycoprotein called GPS or glycocalicin is a prerequisite to the agglutination of human platelets by bovine factor VIII related protein.

scholarly journals Characterization of human platelet glycoprotein antigens giving rise to individual immunoprecipitates in crossed-immunoelectrophoresis

Blood ◽  
1981 ◽  
Vol 58 (6) ◽  
pp. 1190-1197 ◽  
Author(s):  
TJ Kunicki ◽  
AT Nurden ◽  
D Pidard ◽  
NR Russell ◽  
JP Caen
Keyword(s):  
Sodium Dodecyl ◽  
Electrophoretic Analysis ◽  
Human Platelets ◽  
Soluble Proteins ◽  
Platelet Glycoprotein ◽  
Membrane Glycoprotein ◽  
Membrane Glycoproteins ◽  
Reference Pattern ◽  
Crossed Immunoelectrophoresis ◽  
Normal Individuals

Abstract Washed human platelets were labeled with 125I by the lactoperoxidase- catalyzed method and solubilized in 1% Triton X-100. The soluble proteins were analyzed by crossed-immunoelectrophoresis in 1% agarose, employing a rabbit antibody raised against whole human platelets. Analysis of autoradiograms developed from dried agarose gels led to the establishment of a normal reference pattern that was consistent for platelets obtained from more than 50 normal individuals. Six platelet membrane glycoprotein antigens contained in four distinguishable precipitates were identified. Each identification was based on direct sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis of 125I-antigens contained in individually excised precipitates. These platelet antigens include major membrane glycoproteins previously designated la, lb, lla, llb, llla, and lllb. Glycoproteins llb and llla were shown to be contained in a single immunoprecipitate, while glycoproteins la and lla were routinely detected in a single different immunoprecipitate. Analysis of soluble proteins from platelets of five patients with Glanzmann's thrombasthenia demonstrated either a complete absence or a marked reduction of only one radiolabeled precipitate, that containing membrane glycoproteins llb and llla. Platelet samples from two patients with Bernard-Soulier syndrome were devoid of a different precipitate, that containing membrane glycoprotein lb.

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