Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.
Surface glycoproteins on platelets which have a key role in hemostasis and thrombosis such as platelet adhesion and aggregation. Many of these are receptors.
The attachment of PLATELETS to one another. This clumping together can be induced by a number of agents (e.g., THROMBIN; COLLAGEN) and is part of the mechanism leading to the formation of a THROMBUS.
A congenital bleeding disorder with prolonged bleeding time, absence of aggregation of platelets in response to most agents, especially ADP, and impaired or absent clot retraction. Platelet membranes are deficient in or have a defect in the glycoprotein IIb-IIIa complex (PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX).
Platelet membrane glycoprotein complex important for platelet adhesion and aggregation. It is an integrin complex containing INTEGRIN ALPHAIIB and INTEGRIN BETA3 which recognizes the arginine-glycine-aspartic acid (RGD) sequence present on several adhesive proteins. As such, it is a receptor for FIBRINOGEN; VON WILLEBRAND FACTOR; FIBRONECTIN; VITRONECTIN; and THROMBOSPONDINS. A deficiency of GPIIb-IIIa results in GLANZMANN THROMBASTHENIA.
Platelet membrane glycoprotein complex essential for normal platelet adhesion and clot formation at sites of vascular injury. It is composed of three polypeptides, GPIb alpha, GPIb beta, and GPIX. Glycoprotein Ib functions as a receptor for von Willebrand factor and for thrombin. Congenital deficiency of the GPIb-IX complex results in Bernard-Soulier syndrome. The platelet glycoprotein GPV associates with GPIb-IX and is also absent in Bernard-Soulier syndrome.
A series of progressive, overlapping events, triggered by exposure of the PLATELETS to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug.
The process whereby PLATELETS adhere to something other than platelets, e.g., COLLAGEN; BASEMENT MEMBRANE; MICROFIBRILS; or other "foreign" surfaces.
The number of PLATELETS per unit volume in a sample of venous BLOOD.
Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products.
Human alloantigens expressed only on platelets, specifically on platelet membrane glycoproteins. These platelet-specific antigens are immunogenic and can result in pathological reactions to transfusion therapy.
A high-molecular-weight plasma protein, produced by endothelial cells and megakaryocytes, that is part of the factor VIII/von Willebrand factor complex. The von Willebrand factor has receptors for collagen, platelets, and ristocetin activity as well as the immunologically distinct antigenic determinants. It functions in adhesion of platelets to collagen and hemostatic plug formation. The prolonged bleeding time in VON WILLEBRAND DISEASES is due to the deficiency of this factor.
An enzyme formed from PROTHROMBIN that converts FIBRINOGEN to FIBRIN.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position.
Antibodies produced by a single clone of cells.
Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.
Univalent antigen-binding fragments composed of one entire IMMUNOGLOBULIN LIGHT CHAIN and the amino terminal end of one of the IMMUNOGLOBULIN HEAVY CHAINS from the hinge region, linked to each other by disulfide bonds. Fab contains the IMMUNOGLOBULIN VARIABLE REGIONS, which are part of the antigen-binding site, and the first IMMUNOGLOBULIN CONSTANT REGIONS. This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN.
Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system.
A CXC chemokine that is found in the alpha granules of PLATELETS. The protein has a molecular size of 7800 kDa and can occur as a monomer, a dimer or a tetramer depending upon its concentration in solution. Platelet factor 4 has a high affinity for HEPARIN and is often found complexed with GLYCOPROTEINS such as PROTEIN C.
Duration of blood flow after skin puncture. This test is used as a measure of capillary and platelet function.
A subnormal level of BLOOD PLATELETS.
An antibiotic mixture of two components, A and B, obtained from Nocardia lurida (or the same substance produced by any other means). It is no longer used clinically because of its toxicity. It causes platelet agglutination and blood coagulation and is used to assay those functions in vitro.
The transfer of blood platelets from a donor to a recipient or reinfusion to the donor.
Laboratory examination used to monitor and evaluate platelet function in a patient's blood.
A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION.
Venoms from snakes of the subfamily Crotalinae or pit vipers, found mostly in the Americas. They include the rattlesnake, cottonmouth, fer-de-lance, bushmaster, and American copperhead. Their venoms contain nontoxic proteins, cardio-, hemo-, cyto-, and neurotoxins, and many enzymes, especially phospholipases A. Many of the toxins have been characterized.
Very large BONE MARROW CELLS which release mature BLOOD PLATELETS.
Platelet membrane glycoprotein IIb is an integrin alpha subunit that heterodimerizes with INTEGRIN BETA3 to form PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX. It is synthesized as a single polypeptide chain which is then postranslationally cleaved and processed into two disulfide-linked subunits of approximately 18 and 110 kDa in size.
Formation and development of a thrombus or blood clot in the blood vessel.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Cell adhesion molecule and CD antigen that mediates the adhesion of neutrophils and monocytes to activated platelets and endothelial cells.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A familial coagulation disorder characterized by a prolonged bleeding time, unusually large platelets, and impaired prothrombin consumption.
Sites on an antigen that interact with specific antibodies.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
An integrin alpha subunit that primarily combines with INTEGRIN BETA1 to form the INTEGRIN ALPHA2BETA1 heterodimer. It contains a domain which has homology to collagen-binding domains found in von Willebrand factor.
A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).
The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
Thin layers of tissue which cover parts of the body, separate adjacent cavities, or connect adjacent structures.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
The rate dynamics in chemical or physical systems.
Amidines substituted with a benzene group. Benzamidine and its derivatives are known as peptidase inhibitors.
An unstable intermediate between the prostaglandin endoperoxides and thromboxane B2. The compound has a bicyclic oxaneoxetane structure. It is a potent inducer of platelet aggregation and causes vasoconstriction. It is the principal component of rabbit aorta contracting substance (RCS).
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
The sum of the weight of all the atoms in a molecule.
Peptides composed of between two and twelve amino acids.
An integrin beta subunit of approximately 85-kDa in size which has been found in INTEGRIN ALPHAIIB-containing and INTEGRIN ALPHAV-containing heterodimers. Integrin beta3 occurs as three alternatively spliced isoforms, designated beta3A-C.
Thin structures that encapsulate subcellular structures or ORGANELLES in EUKARYOTIC CELLS. They include a variety of membranes associated with the CELL NUCLEUS; the MITOCHONDRIA; the GOLGI APPARATUS; the ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
The process of the interaction of BLOOD COAGULATION FACTORS that results in an insoluble FIBRIN clot.
Any form of purpura in which the PLATELET COUNT is decreased. Many forms are thought to be caused by immunological mechanisms.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
Proteins prepared by recombinant DNA technology.
Glycoproteins found on the membrane or surface of cells.
A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.
Thrombocytopenia occurring in the absence of toxic exposure or a disease associated with decreased platelets. It is mediated by immune mechanisms, in most cases IMMUNOGLOBULIN G autoantibodies which attach to platelets and subsequently undergo destruction by macrophages. The disease is seen in acute (affecting children) and chronic (adult) forms.
A quality of cell membranes which permits the passage of solvents and solutes into and out of cells.
The process which spontaneously arrests the flow of BLOOD from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements (eg. ERYTHROCYTE AGGREGATION), and the process of BLOOD COAGULATION.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).
Established cell cultures that have the potential to propagate indefinitely.
A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
The deformation and flow behavior of BLOOD and its elements i.e., PLASMA; ERYTHROCYTES; WHITE BLOOD CELLS; and BLOOD PLATELETS.
The semi-permeable outer structure of a red blood cell. It is known as a red cell 'ghost' after HEMOLYSIS.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
Adherence of cells to surfaces or to other cells.
Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.
Fibrinolysin or agents that convert plasminogen to FIBRINOLYSIN.
Collagen receptors are cell surface receptors that modulate signal transduction between cells and the EXTRACELLULAR MATRIX. They are found in many cell types and are involved in the maintenance and regulation of cell shape and behavior, including PLATELET ACTIVATION and aggregation, through many different signaling pathways and differences in their affinities for collagen isoforms. Collagen receptors include discoidin domain receptors, INTEGRINS, and glycoprotein VI.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A dual specificity phosphatase subtype that plays a role in intracellular signal transduction by inactivating MITOGEN-ACTIVATED PROTEIN KINASES. It has specificity for EXTRACELLULAR SIGNAL-REGULATED MAP KINASES and is primarily localized to the CELL NUCLEUS.
Bleeding or escape of blood from a vessel.
Artificially produced membranes, such as semipermeable membranes used in artificial kidney dialysis (RENAL DIALYSIS), monomolecular and bimolecular membranes used as models to simulate biological CELL MEMBRANES. These membranes are also used in the process of GUIDED TISSUE REGENERATION.
A phospholipid from the platelet membrane that contributes to the blood clotting cascade by forming a phospholipid-protein complex (THROMBOPLASTIN) which serves as a cofactor with FACTOR VIIA to activate FACTOR X in the extrinsic pathway of BLOOD COAGULATION.
Synthetic compounds that are analogs of the naturally occurring prostaglandin endoperoxides and that mimic their pharmacologic and physiologic activities. They are usually more stable than the naturally occurring compounds.
A subclass of purinergic P2Y receptors that have a preference for ADP binding and are coupled to GTP-BINDING PROTEIN ALPHA SUBUNIT, GI. The P2Y12 purinergic receptors are found in PLATELETS where they play an important role regulating PLATELET ACTIVATION.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase.
The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.
Group of hemorrhagic disorders in which the VON WILLEBRAND FACTOR is either quantitatively or qualitatively abnormal. They are usually inherited as an autosomal dominant trait though rare kindreds are autosomal recessive. Symptoms vary depending on severity and disease type but may include prolonged bleeding time, deficiency of factor VIII, and impaired platelet adhesion.
A family of related, adhesive glycoproteins which are synthesized, secreted, and incorporated into the extracellular matrix of a variety of cells, including alpha granules of platelets following thrombin activation and endothelial cells. They interact with a number of BLOOD COAGULATION FACTORS and anticoagulant factors. Five distinct forms have been identified, thrombospondin 1, -2, -3, -4, and cartilage oligomeric matrix protein (COMP). They are involved in cell adhesion, platelet aggregation, cell proliferation, angiogenesis, tumor metastasis, VASCULAR SMOOTH MUSCLE growth, and tissue repair.
The relationship between the dose of an administered drug and the response of the organism to the drug.
CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.
A family of transmembrane glycoproteins (MEMBRANE GLYCOPROTEINS) consisting of noncovalent heterodimers. They interact with a wide variety of ligands including EXTRACELLULAR MATRIX PROTEINS; COMPLEMENT, and other cells, while their intracellular domains interact with the CYTOSKELETON. The integrins consist of at least three identified families: the cytoadhesin receptors(RECEPTORS, CYTOADHESIN), the leukocyte adhesion receptors (RECEPTORS, LEUKOCYTE ADHESION), and the VERY LATE ANTIGEN RECEPTORS. Each family contains a common beta-subunit (INTEGRIN BETA CHAINS) combined with one or more distinct alpha-subunits (INTEGRIN ALPHA CHAINS). These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development; HEMOSTASIS; THROMBOSIS; WOUND HEALING; immune and nonimmune defense mechanisms; and oncogenic transformation.
Disorders caused by abnormalities in platelet count or function.
Condensed areas of cellular material that may be bounded by a membrane.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Elements of limited time intervals, contributing to particular results or situations.
Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.
Immunoelectrophoresis in which a second electrophoretic transport is performed on the initially separated antigen fragments into an antibody-containing medium in a direction perpendicular to the first electrophoresis.
Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.
The motion of phospholipid molecules within the lipid bilayer, dependent on the classes of phospholipids present, their fatty acid composition and degree of unsaturation of the acyl chains, the cholesterol concentration, and temperature.
Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
Techniques for removal by adsorption and subsequent elution of a specific antibody or antigen using an immunosorbent containing the homologous antigen or antibody.
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
Receptors such as INTEGRIN ALPHAVBETA3 that bind VITRONECTIN with high affinity and play a role in cell migration. They also bind FIBRINOGEN; VON WILLEBRAND FACTOR; osteopontin; and THROMBOSPONDINS.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)
A chromatographic technique that utilizes the ability of biological molecules to bind to certain ligands specifically and reversibly. It is used in protein biochemistry. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
A protein derived from FIBRINOGEN in the presence of THROMBIN, which forms part of the blood clot.
The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A family of proteinase-activated receptors that are specific for THROMBIN. They are found primarily on PLATELETS and on ENDOTHELIAL CELLS. Activation of thrombin receptors occurs through the proteolytic action of THROMBIN, which cleaves the N-terminal peptide from the receptor to reveal a new N-terminal peptide that is a cryptic ligand for the receptor. The receptors signal through HETEROTRIMERIC GTP-BINDING PROTEINS. Small synthetic peptides that contain the unmasked N-terminal peptide sequence can also activate the receptor in the absence of proteolytic activity.
Cell surface proteins that bind THROMBOXANES with high affinity and trigger intracellular changes influencing the behavior of cells. Some thromboxane receptors act via the inositol phosphate and diacylglycerol second messenger systems.
Layers of protein which surround the capsid in animal viruses with tubular nucleocapsids. The envelope consists of an inner layer of lipids and virus specified proteins also called membrane or matrix proteins. The outer layer consists of one or more types of morphological subunits called peplomers which project from the viral envelope; this layer always consists of glycoproteins.
The process of generating thrombocytes (BLOOD PLATELETS) from the pluripotent HEMATOPOIETIC STEM CELLS in the BONE MARROW via the MEGAKARYOCYTES. The humoral factor with thrombopoiesis-stimulating activity is designated THROMBOPOIETIN.
Endogenous substances, usually proteins, that are involved in the blood coagulation process.
Disorder characterized by a decrease or lack of platelet dense bodies in which the releasable pool of adenine nucleotides and 5HT are normally stored.
A stable prostaglandin endoperoxide analog which serves as a thromboxane mimetic. Its actions include mimicking the hydro-osmotic effect of VASOPRESSIN and activation of TYPE C PHOSPHOLIPASES. (From J Pharmacol Exp Ther 1983;224(1): 108-117; Biochem J 1984;222(1):103-110)
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Agents that prevent clotting.
Coagulation of blood in any of the CORONARY VESSELS. The presence of a blood clot (THROMBUS) often leads to MYOCARDIAL INFARCTION.
The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction.
A 44-kDa highly glycosylated plasma protein that binds phospholipids including CARDIOLIPIN; APOLIPOPROTEIN E RECEPTOR; membrane phospholipids, and other anionic phospholipid-containing moieties. It plays a role in coagulation and apoptotic processes. Formerly known as apolipoprotein H, it is an autoantigen in patients with ANTIPHOSPHOLIPID ANTIBODIES.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension (HYPERTENSION, PULMONARY).
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
A chelating agent that sequesters a variety of polyvalent cations such as CALCIUM. It is used in pharmaceutical manufacturing and as a food additive.
Local surface sites on antibodies which react with antigen determinant sites on antigens (EPITOPES.) They are formed from parts of the variable regions of FAB FRAGMENTS.
A calcium-activated enzyme that catalyzes the hydrolysis of ATP to yield AMP and orthophosphate. It can also act on ADP and other nucleoside triphosphates and diphosphates. EC
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes.
An integrin found on fibroblasts, platelets, endothelial and epithelial cells, and lymphocytes where it functions as a receptor for COLLAGEN and LAMININ. Although originally referred to as the collagen receptor, it is one of several receptors for collagen. Ligand binding to integrin alpha2beta1 triggers a cascade of intracellular signaling, including activation of p38 MAP kinase.
Transport proteins that carry specific substances in the blood or across cell membranes.
Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.
Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to the hexahydroxy alcohol, myo-inositol. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid, myo-inositol, and 2 moles of fatty acids.
Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.
A humoral factor that stimulates the production of thrombocytes (BLOOD PLATELETS). Thrombopoietin stimulates the proliferation of bone marrow MEGAKARYOCYTES and their release of blood platelets. The process is called THROMBOPOIESIS.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
A darkly stained mat-like EXTRACELLULAR MATRIX (ECM) that separates cell layers, such as EPITHELIUM from ENDOTHELIUM or a layer of CONNECTIVE TISSUE. The ECM layer that supports an overlying EPITHELIUM or ENDOTHELIUM is called basal lamina. Basement membrane (BM) can be formed by the fusion of either two adjacent basal laminae or a basal lamina with an adjacent reticular lamina of connective tissue. BM, composed mainly of TYPE IV COLLAGEN; glycoprotein LAMININ; and PROTEOGLYCAN, provides barriers as well as channels between interacting cell layers.
Microscopy in which the object is examined directly by an electron beam scanning the specimen point-by-point. The image is constructed by detecting the products of specimen interactions that are projected above the plane of the sample, such as backscattered electrons. Although SCANNING TRANSMISSION ELECTRON MICROSCOPY also scans the specimen point by point with the electron beam, the image is constructed by detecting the electrons, or their interaction products that are transmitted through the sample plane, so that is a form of TRANSMISSION ELECTRON MICROSCOPY.
The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm.
NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)
An ionophorous, polyether antibiotic from Streptomyces chartreusensis. It binds and transports CALCIUM and other divalent cations across membranes and uncouples oxidative phosphorylation while inhibiting ATPase of rat liver mitochondria. The substance is used mostly as a biochemical tool to study the role of divalent cations in various biological systems.
The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)
A group of physiologically active prostaglandin endoperoxides. They are precursors in the biosynthesis of prostaglandins and thromboxanes. The most frequently encountered member of this group is the prostaglandin H2.
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
A purely physical condition which exists within any material because of strain or deformation by external forces or by non-uniform thermal expansion; expressed quantitatively in units of force per unit area.
Venoms from SNAKES of the viperid family. They tend to be less toxic than elapid or hydrophid venoms and act mainly on the vascular system, interfering with coagulation and capillary membrane integrity and are highly cytotoxic. They contain large amounts of several enzymes, other factors, and some toxins.
A preparation consisting of PLATELETS concentrated in a limited volume of PLASMA. This is used in various surgical tissue regeneration procedures where the GROWTH FACTORS in the platelets enhance wound healing and regeneration.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
Precordial pain at rest, which may precede a MYOCARDIAL INFARCTION.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)
Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
Single-chain polypeptides of about 65 amino acids (7 kDa) from LEECHES that have a neutral hydrophobic N terminus, an acidic hydrophilic C terminus, and a compact, hydrophobic core region. Recombinant hirudins lack tyr-63 sulfation and are referred to as 'desulfato-hirudins'. They form a stable non-covalent complex with ALPHA-THROMBIN, thereby abolishing its ability to cleave FIBRINOGEN.
The process by which blood or its components are kept viable outside of the organism from which they are derived (i.e., kept from decay by means of a chemical agent, cooling, or a fluid substitute that mimics the natural state within the organism).
A condition in newborns caused by immunity of the mother to PLATELET ALLOANTIGENS on the fetal platelets. The PLATELETS, coated with maternal ANTIBODIES, are destroyed and removed by the fetal MONONUCLEAR PHAGOCYTE SYSTEM. Affected infants may have INTRACRANIAL HEMORRHAGES.
A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.
The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.
Leukocyte differentiation antigens and major platelet membrane glycoproteins present on MONOCYTES; ENDOTHELIAL CELLS; PLATELETS; and mammary EPITHELIAL CELLS. They play major roles in CELL ADHESION; SIGNAL TRANSDUCTION; and regulation of angiogenesis. CD36 is a receptor for THROMBOSPONDINS and can act as a scavenger receptor that recognizes and transports oxidized LIPOPROTEINS and FATTY ACIDS.
A dye which inhibits protein biosynthesis at the initial stages. The ammonium salt (aluminon) is a reagent for the colorimetric estimation of aluminum in water, foods, and tissues.
Proteins which contain carbohydrate groups attached covalently to the polypeptide chain. The protein moiety is the predominant group with the carbohydrate making up only a small percentage of the total weight.
Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.
Increased numbers of platelets in the peripheral blood. (Dorland, 27th ed)
Chemical groups containing the covalent disulfide bonds -S-S-. The sulfur atoms can be bound to inorganic or organic moieties.
A subclass of eicosanoid receptors that have specificity for THROMBOXANE A2 and PROSTAGLANDIN H2.
A phenomenon in which the surface of a liquid where it contacts a solid is elevated or depressed, because of the relative attraction of the molecules of the liquid for each other and for those of the solid. (from McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
A serine endopeptidase that is formed from TRYPSINOGEN in the pancreas. It is converted into its active form by ENTEROPEPTIDASE in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC
The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)
Dilation of an occluded coronary artery (or arteries) by means of a balloon catheter to restore myocardial blood supply.
A genus of the subfamily CERCOPITHECINAE, family CERCOPITHECIDAE, consisting of five named species: PAPIO URSINUS (chacma baboon), PAPIO CYNOCEPHALUS (yellow baboon), PAPIO PAPIO (western baboon), PAPIO ANUBIS (or olive baboon), and PAPIO HAMADRYAS (hamadryas baboon). Members of the Papio genus inhabit open woodland, savannahs, grassland, and rocky hill country. Some authors consider MANDRILLUS a subgenus of Papio.
A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC, it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.
Azoles with an OXYGEN and a NITROGEN next to each other at the 1,2 positions, in contrast to OXAZOLES that have nitrogens at the 1,3 positions.
Peptides whose amino and carboxy ends are linked together with a peptide bond forming a circular chain. Some of them are ANTI-INFECTIVE AGENTS. Some of them are biosynthesized non-ribosomally (PEPTIDE BIOSYNTHESIS, NON-RIBOSOMAL).
Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.
A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases IMMUNITY, and provides energy for muscle tissue, BRAIN, and the CENTRAL NERVOUS SYSTEM.
Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis.
A lipoxygenase metabolite of ARACHIDONIC ACID. It is a highly selective ligand used to label mu-opioid receptors in both membranes and tissue sections. The 12-S-HETE analog has been reported to augment tumor cell metastatic potential through activation of protein kinase C. (J Pharmacol Exp Ther 1995; 274(3):1545-51; J Natl Cancer Inst 1994; 86(15):1145-51)
Chromatography on non-ionic gels without regard to the mechanism of solute discrimination.
The number of LEUKOCYTES and ERYTHROCYTES per unit volume in a sample of venous BLOOD. A complete blood count (CBC) also includes measurement of the HEMOGLOBIN; HEMATOCRIT; and ERYTHROCYTE INDICES.
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES.
Cell surface receptors that bind prostaglandins with high affinity and trigger intracellular changes which influence the behavior of cells. Prostaglandin receptor subtypes have been tentatively named according to their relative affinities for the endogenous prostaglandins. They include those which prefer prostaglandin D2 (DP receptors), prostaglandin E2 (EP1, EP2, and EP3 receptors), prostaglandin F2-alpha (FP receptors), and prostacyclin (IP receptors).
A family of crosslinking filament proteins encoded by distinct FLN genes. Filamins are involved in cell adhesion, spreading, and migration, acting as scaffolds for over 90 binding partners including channels, receptors, intracellular signaling molecules and transcription factors. Due to the range of molecular interactions, mutations in FLN genes result in anomalies with moderate to lethal consequences.
Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.
Fatty acid derivatives of glycerophosphates. They are composed of glycerol bound in ester linkage with 1 mole of phosphoric acid at the terminal 3-hydroxyl group and with 2 moles of fatty acids at the other two hydroxyl groups.
A serine endopeptidase secreted by the pancreas as its zymogen, CHYMOTRYPSINOGEN and carried in the pancreatic juice to the duodenum where it is activated by TRYPSIN. It selectively cleaves aromatic amino acids on the carboxyl side.
A metallic element, atomic number 49, atomic weight 114.82, symbol In. It is named from its blue line in the spectrum. (From Dorland, 28th ed)
A characteristic symptom complex.
Platelet aggregation is achieved by mediating expression of the glycoprotein complex GP IIb/IIIa in the cell membrane of ... Circulating fibrinogen binds these receptors on adjacent platelets, further strengthening the clot. It is believed that the ... and humans". Drug Metabolism and Disposition. 28 (8): 973-80. PMID 10901709. Coxib and traditional NSAID Trialists' (CNT) ... Thromboxane A2 (TXA2), produced by activated platelets, has prothrombotic properties, stimulating activation of new platelets ...
... the platelets are joined by vWF due to its ability to bind the activated GPIIb / IIIa complex. This transmembrane glycoprotein ... This complex is located mainly on endothelial cells but also on smooth muscle cells, macrophages and platelets. Its main ... and functional studies of human and mouse glycoprotein VI: a platelet-specific collagen receptor from the immunoglobulin ... In consequence, this complex activates GPIIb / IIIa membrane glycoproteins, allowing them to bind fibrinogen. Fibrinogen ...
Platelet aggregation is achieved by mediating expression of the glycoprotein complex GP IIb/IIIa in the cell membrane of ... Circulating fibrinogen binds these receptors on adjacent platelets, further strengthening the clot. ... and humans". Drug Metabolism and Disposition. 28 (8): 973-80. PMID 10901709.. ... Role of A2 in platelet aggregation[edit]. Thromboxane A2 (TXA2), produced by activated platelets, has prothrombotic properties ...
... activated platelets with exposed GPIIb/IIIa can bind fibrinogen to aggregate. GPIIb/IIIa may also further anchor the platelets ... These changes are all brought about by the interaction of the microtubule/actin complex with the platelet cell membrane and ... is rich in glycoproteins required for platelet adhesion, activation, and aggregation. For example, GPIb/IX/X; GPVI; GPIIb/IIIa. ... Scanning electron micrograph of blood cells. From left to right: human erythrocyte, activated platelet, leukocyte. ...
1995). "Expression of platelet membrane glycoprotein V in human megakaryocytes and megakaryocytic cell lines: a study using a ... 1997). "Human kininogens regulate thrombin binding to platelets through the glycoprotein Ib-IX-V complex". Blood. 90 (4): 1508- ... and GPIIb/IIIa are implicated in expression of thrombin-induced platelet procoagulant activity". Thromb. Haemost. 86 (4): 1065- ... Glycoprotein V (platelet) (GP5) also known as CD42d (Cluster of Differentiation 42d), is a human gene. Human platelet ...
... activated platelets with exposed GPIIb/IIIa can bind fibrinogen to aggregate. GPIIb/IIIa may also further anchor the platelets ... These changes are all brought about by the interaction of the microtubule/actin complex with the platelet cell membrane and ... is rich in glycoproteins required for platelet adhesion, activation and aggregation. For example, GPIb/IX/V; GPVI; GPIIb/IIIa. ... platelet life span, and platelet function in healthy human volunteers". Blood. 95 (8): 2514-22. doi:10.1182/blood.V95.8.2514. ...
... blood platelets through binding to their GpIIb/IIIa surface membrane fibrinogen receptor. Fibrin participates in limiting blood ... Fibrinogen (factor I) is a glycoprotein complex, made in the liver, that circulates in the blood of all vertebrates. During ... Fibrin also mediates blood platelet and endothelial cell spreading, tissue fibroblast proliferation, capillary tube formation, ... All three genes are located on the long or "q" arm of human chromosome 4 (at positions 4q31.3, 4q31.3, and 4q32.1, respectively ...
This localization of platelets to the extracellular matrix promotes collagen interaction with platelet glycoprotein VI. Binding ... It is characterized by a defect in GPIIb/IIIa fibrinogen receptor complex. When GPIIb/IIIa receptor is dysfunctional, ... PLA2 then modifies the integrin membrane glycoprotein IIb/IIIa, increasing its affinity to bind fibrinogen. The activated ... Protein C is activated in a sequence that starts with Protein C and thrombin binding to a cell surface protein thrombomodulin. ...
Localization of the domain actin-binding protein that binds to glycoprotein Ib and actin in human platelets. J Biol Chem. 1988 ... D3 phosphoinositides and outside-in integrin signaling by GPIIb/IIIa mediate platelet actin assembly and filopodial extension ... Filamin A, the Arp2/3 complex, and the morphology and function of cortical actin filaments in human melanoma cells. J Cell Biol ... Association of gelsolin with actin filaments and with cell membranes of macrophages and platelets. J Cell Biol. 1989; 108:467- ...
"Entrez Gene: ITGA2B integrin, alpha 2b (platelet glycoprotein IIb of IIb/IIIa complex, antigen CD41)".. ... membrane. • external side of plasma membrane. • extracellular exosome. • plasma membrane. • blood microparticle. • cell surface ... protein binding. • fibrinogen binding. • extracellular matrix binding. • identical protein binding. • metal ion binding. ... Integrin alpha-IIb is a protein that in humans is encoded by the ITGA2B gene. ITGA2B, also known as CD41, encodes integrin ...
... a heterodimer consisting of the plasma-membrane glycoproteins (GP) IIb and IIIa. Although the GPIIb-IIIa complex is present on ... We found that the immunogold-labeled GPIIb-IIIa was monodispersed over the surface of unstimulated platelets, although the cell ... as well as thrombin-activated and ADP-activated human platelets. ... bound to GPIIb-IIIa on the cell surface and was similarly ... On thrombin-stimulated platelets, approximately 65% of the GPIIb-IIIa molecules were in clusters within the plane of the ...
Platelet aggregation is achieved by mediating expression of the glycoprotein complex GP IIb/IIIa in the cell membrane of ... Circulating fibrinogen binds these receptors on adjacent platelets, further strengthening the clot. It is believed that the ... and humans". Drug Metabolism and Disposition. 28 (8): 973-80. PMID 10901709. Coxib and traditional NSAID Trialists (CNT) ... Thromboxane A2 (TXA2), produced by activated platelets, has prothrombotic properties, stimulating activation of new platelets ...
... the platelets are joined by vWF due to its ability to bind the activated GPIIb / IIIa complex. This transmembrane glycoprotein ... This complex is located mainly on endothelial cells but also on smooth muscle cells, macrophages and platelets. Its main ... and functional studies of human and mouse glycoprotein VI: a platelet-specific collagen receptor from the immunoglobulin ... In consequence, this complex activates GPIIb / IIIa membrane glycoproteins, allowing them to bind fibrinogen. Fibrinogen ...
Platelet aggregation is achieved by mediating expression of the glycoprotein complex GP IIb/IIIa in the cell membrane of ... Circulating fibrinogen binds these receptors on adjacent platelets, further strengthening the clot. ... and humans". Drug Metabolism and Disposition. 28 (8): 973-80. PMID 10901709.. ... Role of A2 in platelet aggregation[edit]. Thromboxane A2 (TXA2), produced by activated platelets, has prothrombotic properties ...
The GP IIb/IIIa complex is an important membrane-bound heterodimeric glycoprotein complex in platelets (approximately 50 000 ... copies per platelet). [0141]At least two series of peptides, corresponding to amino acid sequences naturally present in human ... foam cells. SRs are membrane-bound surface proteins capable of binding senescent cells and also chemically or biologically ... When the platelets are activated, the GP IIb/IIIa glycoprotein receptors which are at the surface of the platelet membranes ...
... activation of adjacent platelets, and conformational changes in the platelet α(IIb)β3 integrin (GP IIb/IIIa receptor). Platelet ... Furthermore, a ~180-kDa sialofucosylated glycoprotein(s) mediated selectin binding in CD44-knockdown cells. This glycoprotein ... Putative outer membrane proteins of Leptospira interrogans stimulate human umbilical vein endothelial cells (HUVECS) and ... Elevated platelet-monocyte complexes in patients with psoriatic arthritis. Platelets 14:1-5CrossRefGoogle Scholar ...
Glycoprotein V (GPV) is a platelet membrane protein present as a subunit of the GPIb/V/IX complex, a major receptor for von ... protein kinase A-dependent phosphorylation of GpIbbeta enhances 14-3-3zeta binding to the GpIb/IX/V complex in human platelets ... leading to platelet activation and the expression of a ligand-receptive GpIIb-IIIa complex. The highly conserved cytoplasmic ... The remodeling of the actin cytoskeleton is essential for cell migration, cell division, and cell morphogenesis. Actin-binding ...
Inhibition of sodium channels prevents the depolarization of nerve cell membranes and inhibits subsequent propagation of ... Dibucaine reversibly binds to and inactivates sodium channels in the neuronal cell membrane. ... Considerable evidence indicates that the glycoprotein (GP) IIb/IIIa complex on human platelets functions as a receptor for… ... an activation-dependent change in the conformation and/or microenvironment of the platelet glycoprotein IIb/IIIa complex. ...
Organization of the glycoprotein (GP) IIb/IIIa heterodimer on resting human platelets studied by flow cytometric energy ... GPI-microdomains (membrane rafts) and signaling of the multi-chain interleukin-2 receptor in human lymphoma/leukemia T cell ... interleukin-9 receptor with interleukin-2 receptor and major histocompatibility complex glycoproteins in human T lymphoma cells ... Multiple binding sites for melatonin on Kv1.3. Varga, Z., Panyi, G., Péter, M., Pieri, C., Csécsei, G., Damjanovich, S. & ...
Expression of platelet membrane glycoprotein V in human megakaryocytes and megakaryocytic cell lines: a study using a novel ... Delineating the roles of the GPIIb/IIIa and GP-Ib-IX-V platelet receptors in mediating platelet adhesion to adsorbed fibrinogen ... MBD5 and MBD6 interact with the human PR-DUB complex through their methyl-CpG-binding domain. Proteomics. (2014) 14:2179-89. ... which could be ascribed to a cell type with reasonable confidence i.e., neutrophils, NK cells, and platelets. These cell types ...
The approaches to localize ligand binding sites on the adhesive receptors include studies on... ... The domains of various integrins involved in the binding to adhesive proteins are poorly characterized. ... relationship between platelet membrane glycoprotein GPIIb/IIIa and cell surface molecules expressed by a variety of cells, Proc ... Preparation of monoclonal antibodies against glycoprotein IIIa of human platelets: Their effect on platelet aggregation, Eur. J ...
Mediator release may occur via cross-linking of cell-bound IgE by... ... Allergic reactions to drugs are not always the result of the drugs protein-binding capacity, biotransformation, or degradation ... the Fab fragment of a chimeric human-mouse monoclonal antibody that binds to the platelet glycoprotein receptor GPIIb/IIIa. ... The BCR has immunoglobulin anchored in the cell membrane, and, in concert with the B cell co-receptor complex, it is the ...
GPIIb/IIIa) complex of platelets. GPIIb/IIIa is the major membrane receptor protein that is key to the role of the platelet ... known that platelet aggregation is mediated by a mechanism involving the binding of fibrinogen to the glycoprotein IIb/IIIa ( ... It also appears to reduce oxLDL-induced apoptosis in human endothelial cells. Oxidation of LDL is a key early step in ... GPIIb/IIIa) complex of platelets. GPIIb/IIIa is the major membrane receptor protein that is key to the role of the platelet ...
... and platelet-platelet cohesion to form large aggregates. Platelet membrane glycoproteins (GP) IIb and IIIa constitute a ... Human platelets participate in a number of adhesive interactions, including binding to exposed subendothelium after vascular ... evidence was obtained that the endothelial cell forms of GPIIb and GPIIIa may exist complexed to one another after ... The platelet glycoprotein IIb/IIIa-like protein in human endothelial cells promotes adhesion but not initial attachment to ...
... activated platelets with exposed GPIIb/IIIa can bind fibrinogen to aggregate. GPIIb/IIIa may also further anchor the platelets ... These changes are all brought about by the interaction of the microtubule/actin complex with the platelet cell membrane and ... is rich in glycoproteins required for platelet adhesion, activation, and aggregation. For example, GPIb/IX/X; GPVI; GPIIb/IIIa. ... Scanning electron micrograph of blood cells. From left to right: human erythrocyte, activated platelet, leukocyte. ...
Association of radiolabeled GPIIb/IIIa antagonists with unactivated human platelets was examined using human PRP. In vitro ... 1986) Platelet membrane glycoprotein IIb/IIIa: Member of a family of RGD specific adhesion receptors. Science (Wash DC) 231: ... toward the platelet GPIIb/IIIa receptors as compared with the closely related vitronectin receptors on endothelial cells or ... antibody reports an activation-dependent change in the conformation and/or microenvironment of the platelet GPIIb/IIIa complex. ...
... are located on the platelet membrane glycoprotein GP IIb/IIIa or GP Ib/IX complex [5]. These complexes can be easily swallowed ... Platelet-bound antibodies were detected with the addition of mouse monoclonal anti-human IgG and human IgG-sensitized ... on the surface of platelets, including GP IIb/IIIa, GP Ib/IX, and GP Ia/IIa; approximately 75% ... Platelet autoantibodies to specific membrane glycoproteins mediate platelet destruction and are a major agent in the ...
... and the endothelial cells lining the blood vessels. The platelets arise from the fragmentation of the cytoplasm of ... The hemostatic system consists of platelets, coagulation factors, ... interacting with subendothelium-bound von Willebrand factor (vWf) via the membrane glycoprotein (GP) Ib complex. This initial ... The platelet GP IIb/IIIa complex mediates platelet-to-platelet interactions (platelet aggregation). On resting platelets, GP ...
1986) The role of platelet membrane glycoproteins Ib and IIb-IIIa in platelet adherence to human artery subendothelium. Br J ... 1981) Endothelial cell surface expression and binding of factor VIII/von Willebrand factor. Am J Pathol 103:304-308. ... the endocardium was graded according to the distribution and nature of adhered platelets positive to GP Ib/IX and GP IIb/IIIa ... avidin-biotinylated horseradish peroxidase complex (Vectastain, Vector Laboratories, Burlingame, California) at a dilution of 1 ...
Platelet Glycoprotein GPIIb-IIIa Complex / genetics* Actions. * Search in PubMed * Search in MeSH ... Results: Analysis of the patients platelets by fluorescence-activated cell sorting demonstrated trace amounts of beta(3), no ... Molecular insight into human platelet antigens: structural and evolutionary conservation analyses offer new perspective to ... Natural and artificial mutations in αIIb integrin lead to a structural deformation of a calcium-binding site. Mansour W, ...
Protein Aliases: CD61; GPIIIa; integrin beta 3 (Cd61); Integrin beta-3; platelet gpIIIa; Platelet membrane glycoprotein IIIa ... protein binding peptide binding identical protein binding vascular endothelial growth factor receptor 2 binding cell adhesion ... to form gpIIb/IIIa. These heterodimeric complexes are responsible for adhesion to extracellular matrix components including ... CD61 is expressed on platelets and megakaryocytes in association with CD41, and on endothelial cells, monocytes, platelets and ...
... which markedly inhibited the interaction among platelets, tumor cells, and endothelial cells in vitro, and reduced the mean ... 1D12 and 2B4 affected the von Willebrand factor (vWF)-GPIbα interaction via binding to GPIbα aa 41-50 and aa 277-290 ... In addition, potential bleeding complication remains an obstacle for the clinical use of anti-platelet agents in cancer therapy ... To validate our findings, we further obtained mouse anti-human GPIbα monoclonal antibody YQ3 through the same approach. ...
Human factor XII binding to the glycoprotein Ib-IX-V complex inhibits thrombin-induced platelet aggregation. J Biol Chem. 2000 ... Primarily, the platelet-specific integrin, αIIbβ3 (GPIIb-IIIa), plays a key role in thrombus formation, by binding vWF, ... One recent article shows that human platelets express the immune cell receptor, semaphorin 4D (Sema4D), and its binding ... Interaction of calmodulin with the cytoplasmic domain of the platelet membrane glycoprotein Ib-IX-V complex. Blood. 2001; 98: ...
... to its platelet receptor and the subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa complex, thereby inhibiting ... selectively inhibits the binding of adenosine diphosphate (ADP) ... studied using intestinal membrane within a Franz diffusion cell ... platelet aggregation. Oral bioavailability of clopidogrel is very low (less than 50%), due to its poor water solubility. The ... Clopidogrel acts by irreversibly modifying the platelet ADP receptor. Consequently, platelets exposed to clopidogrel are ...
... initially described thrombasthenia in 1918 when he noted purpuric bleeding in patients with normal platelet counts. The term ... This binding adheres platelets to the site of injury. Fibrinogen and vWF bind to the GP IIb-IIIa complex exposed on the ... GT is a rare autosomal recessive disorder whereby the quantity or quality of platelet membrane glycoprotein (GP) IIb-IIIa is ... The deficiency is uniformly present throughout the platelet population and is present in endothelial cells and precursor ...
... binding to its platelet P2Y12 receptor and subsequently the ADP-mediated activation of the glycoprotein GPIIb/IIIa complex, ... The drug is an irreversible inhibitor of the P2Y12 adenosine diphosphate receptor found on the membranes of platelet cells. ... its impaired activation prevents fibrinogen binding to platelets and inhibits platelet aggregation. By blocking the ... Following an oral dose of 14C-labeled clopidogrel in humans, approximately 50% of total radioactivity was excreted in urine and ...
Blood Platelets - drug effects , Phosphinic Acids - chemical synthesis , Binding Sites , Platelet Glycoprotein GPIIb-IIIa ... Humans , Cell Membrane Permeability , Models, Molecular , Structure-Activity Relationship , Static Electricity , Platelet ... Glycoprotein GPIIb-IIIa Complex - antagonists & inhibitors , Platelet Aggregation Inhibitors - chemical synthesis , ... Peptide binding , Molecular chaperone , BINDING-SPECIFICITY , antigen presentation , DENDRITIC CELLS , anti-tumor T cell ...
The platelet GP IIb/IIIa complex mediates platelet-to-platelet interactions (platelet aggregation). On resting platelets, GP ... interacting with subendothelium-bound von Willebrand factor (vWf) via the membrane glycoprotein (GP) Ib complex. This initial ... The platelet count is low, but, characteristically, the platelets are large, often the size of red blood cells, and may be ... Most individuals have leucine at position 33 (PLA1/PLA1 or human platelet alloantigen [HPA]-1a). A small number of individuals ...
Adjacent platelets are also cross-linked through GP IIb/IIIa-fibinogen-GP IIb/IIIa complexes. The membrane of the platelet ... Recombinant human factor VIIa is a vitamin K dependent glycoprotein. The structure of the recombinant factor VIIa is similar to ... The GP IIb/IIIa complex plays an important part in the binding of platelets to endothelium as well as to each other. The ... Treatment was as follows: 27 bags of platelet concentrate, 6 bags of platelet from apheresis, and 7 bags of red blood cell ...
Expression of platelet membrane glycoproteins and α-granule proteins by a human erythroleukemia cell line (HEL). EMBO J. 1984;3 ... We then tested whether the ploidy distribution of the cells expressing only GPIIb-IIIa was different from that of GPIIb-IIIa/ ... the membrane-bound GPV was only detected on 25% of the cells (Figure3A). Almost all the GPIIb+ cells were also stained ... of the cells were positive for GPIIb. The GPIIb labeling did not correspond to background generated by residual platelets ...
  • To determine whether the receptors clustered before ligand binding, or as a consequence thereof, we studied the surface distribution of GPIIb-IIIa after stimulation with ADP, which causes activation of the fibrinogen receptor function of GPIIb-IIIa without inducing the release of fibrinogen. (
  • In the absence of added fibrinogen, the unoccupied, yet binding-competent receptors on ADP-stimulated platelets were monodispersed. (
  • Thromboxane acts by binding to any of the thromboxane receptors, G-protein-coupled receptors coupled to the G protein Gq. (
  • Circulating fibrinogen binds these receptors on adjacent platelets, further strengthening the clot. (
  • Membrane glycoproteins GPIa/IIa, GPVI and probably GPIV as well, function as collagen receptors, engaged in platelet adhesion to collagen. (
  • XV459 represents a potent antiplatelet agent in inhibiting platelet aggregation along with offering high affinity and a relatively slow dissociation rate from human platelet GPIIb/IIIa receptors that might allow for once-a-day p.o. dosage. (
  • These complexes can be easily swallowed and destroyed by the reticuloendothelial system by binding to Fcγ receptors expressed on monocytes and macrophages, leading to a diminished peripheral platelet count [ 7 ]. (
  • The platelet plasma membrane is literally at the cutting-edge of recent research into proteolytic regulation of the function and surface expression of platelet receptors, revealing new mechanisms for how the thrombotic propensity of platelets is controlled in health and disease. (
  • In this review, platelet receptor shedding will be discussed in terms of (1) the identity of proteinases involved in receptor proteolysis, (2) key platelet receptors regulated by proteolytic pathways, and (3) how shedding might be regulated in normal physiology or future therapeutics. (
  • This review focuses on proteolytic pathways that regulate the function and surface expression of platelet receptors involved in hemostasis and thrombotic disease such as heart attack or stroke. (
  • In particular, platelet-specific receptors, glycoprotein (GP)VI and the GPIb-IX-V complex that bind collagen or von Willebrand factor (vWF), respectively, form a physical and functional complex 1 initiating platelet thrombus formation at high shear stress in flowing blood. (
  • The endogenous platelet-surface sheddases that cleave GPVI and/or other platelet receptors are also being revealed. (
  • Using GPVI as the main example, this review will discuss recent studies on proteolytic pathways in platelets with respect to (1) the proteinases involved, (2) key adhesion receptors, and (3) how both receptors and proteinases might be regulated. (
  • Members of 2 main families of proteinases are expressed on the cell surface, the ADAM family of metalloproteinase-disintegrins and the MMP family of matrix metalloproteinases, and may act as sheddases by cleaving the ectodomain of surface receptors. (
  • One of the major families of intracellular enzymes involved in regulating platelet surface receptors is the cysteinyl proteinase, calpain. (
  • Approximately 80,000 GP IIb-IIIa receptors are present on the surface of each platelet. (
  • Other defects in platelet GPIa/IIa (a2b1) and GPVI, as well as isolated defects in agonist receptors or proteins involved in signal transduction may also produce hemorrhagic symptoms, but these disorders are less well characterized. (
  • Megakaryocytic differentiation is accompanied by changes in cell morphology, notably an increase in size and the appearance of demarcation membranes, and by the sequential expression of a number of genes coding for specific cell surface markers, cytokines, and cytokine receptors. (
  • [2] [3] Platelet activation by ADP (blocked by clopidogrel ) leads to the aforementioned conformational change in platelet gpIIb/IIIa receptors that induces binding to fibrinogen. (
  • These then bind their respective receptors on platelet surfaces, in both an autocrine and paracrine fashion (binds both itself and other platelets). (
  • The binding of these receptors result in a cascade of events resulting in an increase in intracellular calcium (e.g. via G q receptor activation leading to Ca 2+ release from platelet endoplasmic reticulum Ca 2+ stores, which may activate PKC). (
  • Two distinct receptors account for recognition of maleyl-albumin in human monocytes during differentiation in vitro. (
  • The characterization and identification of new bacterial effectors and the host cell receptors involved will undoubtedly lead to new discoveries with beneficial purposes. (
  • Different receptors and mechanisms involved in S. aureus internalization into nonprofessional phagocytic cells. (
  • We offer a variety of fluorescent and fluorogenic ligands that bind to membrane receptors and are subsequently internalized. (
  • When soluble or surface-bound IgG immune complexes interact with Fc receptors on phagocytic cells, a number of host defense mechanisms are activated, including phagocytosis and activation of an NADPH oxidase-mediated oxidative burst. (
  • Additional information: Clone REA386 displays negligible binding to Fc receptors. (
  • 9-11 Another potential consequence of this conformational change is the induction of outside-in signaling, which is a common mechanism used by cells to detect ligand binding to integrin receptors. (
  • The platelets of GT 'variants' have normal or near normal (60-100%) expression of dysfunctional receptors. (
  • Although the major receptors and counter receptors have been identified, it remains poorly understood how heterotypic platelet-neutrophil interactions are regulated under disease conditions. (
  • Although neutrophils and platelets preferentially adhere to the site of vascular injury under low and high shear conditions, respectively, the receptors and counter receptors for heterotypic cell-cell interactions are similar under both conditions [ 16 ]. (
  • Hemostasis and pathological thrombus formation are dynamic processes that require a co-ordinated series of events involving platelet membrane receptors, bidirectional intracellular signals, and release of platelet proteins and inflammatory substances. (
  • This review aims to summarize current knowledge in the key steps in the dynamics of thrombus formation, with special emphasis on the crucial participation of platelet receptors and signaling in this process. (
  • Initial tethering and firm adhesion of platelets to the exposed subendothelium is mediated by glycoprotein (GP) Ib/IX/V complex and collagen receptors, GP VI and α 2 β 1 integrin, in the platelet surface, and by VWF and fibrillar collagen in the vascular site. (
  • The best known contact-dependent signaling is outside-in signaling through α Ib β 3 , but new ones are being clarified such as those mediated by interaction of Eph receptors with ephrins, or by Sema 4D and Gas-6 binding to their receptors. (
  • Platelet receptors are at the forefront of recent research and major advances have been made in understanding their molecular functions and their downstream signaling pathways. (
  • Studies with animal models, including pharmacological inhibition and knocking out of nearly all known receptors, adhesion molecules, and many signaling molecules have helped to reveal new mechanisms for how the thrombotic and hemorrhagic propensity of platelets is controlled in health and disease. (
  • Many of these receptors are shared by other cell types, but some are only expressed on platelets. (
  • Nowadays, it is well established that the major platelet receptors have a prominent role in the hemostatic function of platelets, allowing specific interactions and functional responses of vascular adhesive proteins and of soluble platelet agonists (Figure 1). (
  • In addition, it is increasingly recognized that a range of receptors are involved in other less well-understood platelet functions such as inflammation, tumor growth and metastasis, or immunological host defense.1 Internally, platelets contain a cytoskeleton, a dense tubular system, few mitochondrias, glycogen granules, dense (δ) and α storage granules and peroxisomes. (
  • collagen through specific platelet membrane collagen receptors. (
  • Platelet adhesion is also facilitated by direct binding to subendothelial collagen through specific platelet membrane collagen receptors. (
  • Adenosine diphosphate (ADP) and thromboxane A2 bind to specific receptors on platelets to amplify their aggregation after plaque rupture. (
  • 2-4 Thrombin activates platelets by cleaving the G protein-coupled, protease (proteinase)-activated receptors PAR1 and PAR4. (
  • platelet receptors, coagulation proteins, and tumor cells interacting in the process of tumorigenesis. (
  • Integrins are a large family of heterodimeric receptors that mediate the adhesive behavior of cells. (
  • A central feature of these receptors is their ability to transduce bidirectional signals into and out of the cell. (
  • Instead, these ECM proteins are recognized by integrins containing the α 3 , α 6 , and α 7 subunits (laminin-binding receptors) or the α 1 , α 2 , α 10 , and an subunits (collagen-binding receptors). (
  • In addition to serving as ECM receptors, some integrins (e.g., integrins of hematopoietic cells) can bind to counter-receptors on other cells, such as intercellular adhesion molecules (ICAMs) and the vascular cell adhesion molecule-i (VCAM-i) (7). (
  • Several small case-control studies have suggested associations between ischemic stroke and polymorphisms of genes that code for coagulation cascade proteins and platelet receptors. (
  • The candidate genes for this study include the gene encoding β-fibrinogen and the genes encoding platelet glycoprotein (GP) receptors Ia/IIa, Ib/IX/V, and IIb/IIIa. (
  • In addition, we studied genes encoding for platelet receptors because of the efficacy of platelet anti-aggregant therapy in preventing first-time and recurrent ischemic strokes. (
  • To study mechanisms, we engineered αIIbβ3 Chinese hamster ovary (CHO) cells to conditionally express talin and protease-activated receptor (PAR) thrombin receptors. (
  • The domains of various integrins involved in the binding to adhesive proteins are poorly characterized. (
  • Abacavir changes the shape of the HLA antigen-binding cleft producing an alteration in the repertoire of self-peptides that bind HLA-B*57:01 and a T cell response to self-proteins. (
  • Furthermore, inhibitory monoclonal antibodies (mAbs) to the identified membrane proteins were used to inhibit the transfer of preexisting TF to platelets. (
  • Synthesis by cultured human umbilical vein endothelial cells of two proteins structurally and immunologically related to platelet membrane glycoproteins IIb and IIIa. (
  • GPIIb/IIIa in activated platelets is known to bind four soluble adhesive proteins: fibrinogen, von Willebrand factor (VWF), fibronectin and vitronectin. (
  • The binding of fibrinogen is mediated in part by the RGD recognition sequence, which is common to the adhesive proteins that bind to GPIIb/IIIa. (
  • Platelet activation allows binding of these proteins, which bridges adjacent platelets. (
  • The alpha granules contain hemostatic proteins such as fibrinogen, vWf, and growth factors (eg, platelet-derived growth factor). (
  • Megakaryocytes (MK) progressively express lineage-restricted proteins, some of which play essential roles in platelet physiology. (
  • Glycoprotein (GP)Ib-V-IX (CD42) and GPIIb (CD41) are examples of MK-specific proteins having receptor properties essential for platelet adhesion and aggregation. (
  • The involvement of platelet membrane proteins in platelet physiologic functions has been illustrated by study of the effect of MAbs against these membrane proteins on platelets. (
  • Bacteria initially adhere to the cell membrane and extracellular matrix substrates through surface proteins (adhesins) [ 17 , 18 ] and are then internalized by different NPPCs. (
  • Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. (
  • While neutrophils attach to the inflamed venules under low blood shear, platelets adhere to activated ECs and sub-endothelial matrix proteins such as collagen and von Willebrand factor (vWF) under high blood shear and then support neutrophil rolling and adhesion as well as platelet accumulation following arterial injury [ 13 - 15 ]. (
  • Integrin αIIbβ3 can also bind other proteins on platelets and in blood as well as proteins within the intricate lattice that forms in the space between cells (extracellular matrix) to ensure proper clot formation and promote wound healing. (
  • A shortage (deficiency) of functional integrin αIIbβ3 prevents sufficient binding of fibrinogen or other proteins, impairing the formation of blood clots. (
  • The overactive integrin αIIbβ3 binds inappropriately to clotting proteins within the cell during the formation of platelets, causing the platelets to become misshapen and large. (
  • The molecular basis of GT is linked to quantitative and/or qualitative abnormalities of αIIbβ3 integrin that mediates binding of the adhesive proteins to attach aggregating platelets and ensure thrombus formation at sites of injury in blood vessels. (
  • In response to plaque disruption, plasma factor VIIa ("a" denotes the activated form of the blood coagulation proteins) binds TF to produce a complex that converts factor X to factor Xa. (
  • A defined structural unit enables de novo design of small-molecule-binding proteins. (
  • In Project 2, Dr.Shattil will continue to develop and utilize strategies to visualize interactions of proteins with platelet integrin alpha lIb beta 3 in living cells and he will analyze the signaling mechanisms of alpha V integrins in vivo in zebrafish. (
  • The integrins are a family of more than 23 heterodimeric transmembrane proteins that mediate cell-cell adhesions as well as cell-substratum adhesions and signal transduction processes. (
  • The extracellular matrix (ECM) is composed of a complex mixture of polysaccharides and large fibrous proteins such as fibronectin, collagen, and laminin. (
  • The ECM is a complex network of polysaccharides and proteins with high molecular weight, such as laminins, collagens, vitronectin, and fibronectin (1, 2). (
  • ECM proteins are secreted and organized by the cells. (
  • For instance, interactions between the parasite protein PfEMP1 and human proteins such as CD36 and inter-cellular adhesion molecule (ICAM-1) expressed in endothelial cells (EC) are critical for sequestration [ 6 ]. (
  • Korte, Dirk 1990-01-01 00:00:00 To investigate whether changes in platelet condition during platelet storage correlate with an altered expression of platelet membrane proteins, the binding of monoclonal antibodies (MoAbs) to fresh platelets was compared with MoAbs' binding to thrombin‐activated platelets and to platelets stored as platelet concentrates. (
  • They contain a variety of bioactive molecules, including proteins, biolipids, and nucleic acids, which can be transferred between cells without direct cell-to-cell contact. (
  • Carlos and Harlan, "Membrane Proteins Involved in Phagocyte Adherence to Endothelium," Immunol. (
  • alphaV (CD51) to form Vitronectin Receptor and alphaIib (CD41) to form gpIIb/IIIa. (
  • CD61 is a 105 kDa glycoprotein that associates with either the alpha 11b integrin (CD41) or the alpha V integrin (CD51) at the cell surface. (
  • CD61 is expressed on platelets and megakaryocytes in association with CD41, and on endothelial cells, monocytes, platelets and osteoclasts in association with CD51. (
  • Cell sorting studies revealed that the CD41 + GPV + population contained 4N and 8N cells at day 7, and was less effective than CD41 + GPV − cells in generating burst-forming units of erythrocytes or MK colonies. (
  • It has been shown that the effects of MAbs to CD41/CD61 and CD42 on platelet aggregation were heterogeneous, reflecting the different molecular basis of these MAbs, including their ligand selectivity and mechanism of platelet functions. (
  • Clone REA386 recognizes the human CD41a antigen, a calcium-dependent complex of CD41/CD61 (GPIIb/IIIa) expressed on normal platelets and megakaryocytes. (
  • The CD41/CD61 complex is a receptor for fibronectin, fibrinogen, von Willebrand factor, vitronectin, and thrombospondin and is required for platelet aggregation and clotting. (
  • Mutations of either CD41 or CD61 in humans causes Glanzmann's thrombasthenia. (
  • However, CD41 expression is downregulated in midgestation embryos, and it is currently thought that CD41 expression on adult hematopoietic stem cells remains switched off throughout adult life. (
  • CD41 is always non-covalently associated with CD61 (platelet GPIIIa, beta 3 integrin), to form the GPIIb-IIIa (CD41/CD61) complex. (
  • CD41 is expressed by platelets, megakaryocytes and by a small subset of CD34+ cells suggesting that CD41/CD61 is the earliest marker of the megakaryocytic lineage. (
  • It has been assigned to the CD41 cluster of differentiation at the 5th International Workshop on human Leucocyte Differentiation Antigens in Boston, in 1993. (
  • Tissue, cells or virus corresponding to Mouse CD41. (
  • Reacts with a calcium-dependent complex of CD41/CD61, a dimer of 90 kDa and 140 kDa present on the membrane of normal platelets and megakaryocytes. (
  • CD41/CD61 is also known as platelet glycoprotein GPIIb/GPIIIa or integrin IIa/3. (
  • CD61 non-covalently associates with CD41 (alpha Ilb integrin) and is expressed by megakaryocytes and platelets. (
  • The CD61/CD41 complex acts as a receptor for such adhesive ligands as fibronectin, fibrinogen and von Willebrand factor during platelet stimulation. (
  • The mouse monoclonal antibody PAC-1 recognizes an extracellular activation-induced conformational epitope PAC-1 on CD41/CD61 complex (gpIIb/IIIa), also known as integrin alpha IIb beta 3, a receptor which mediates platelet aggregation. (
  • The binding of von Willebrand factor (vWF) results in conformational changes within the GPIb-V-IX complex. (
  • The GPIbα subunit bears the binding site for von Willebrand factor (vWF), α-thrombin, leukocyte integrin αMβ2 and P-selectin. (
  • The α2 subunit includes a domain homologous to von Willebrand factor domain binding to collagen. (
  • Platelets play a primary role in this process, interacting with subendothelium-bound von Willebrand factor (vWf) via the membrane glycoprotein (GP) Ib complex. (
  • We investigated immunoreactive von Willebrand factor (vWF), a platelet adhesion molecule, in the endocardial endothelium and its relationship to thrombogenesis in the human atrial appendage. (
  • Platelet adhesion to the deendothelialized vessel wall is an initiating event of thrombus formation (7) and is mediated through the platelet adhesion molecule von Willebrand factor (vWF) present in the plasma and/or subendothelium (8-10) . (
  • These heterodimeric complexes are responsible for adhesion to extracellular matrix components including fibrinogen, fibronectin, fibronectin, vitronectin, thrombospondin and von Willebrand factor. (
  • CD61 antigen plays a role in platelet aggregation and also as a receptor for fibrinogen, fibronectin, von Willebrand factor and vitronectrin. (
  • 1D12 and 2B4 affected the von Willebrand factor (vWF)-GPIbα interaction via binding to GPIbα aa 41-50 and aa 277-290 respectively, which markedly inhibited the interaction among platelets, tumor cells, and endothelial cells in vitro, and reduced the mean number of surface nodules in the experimental and spontaneous metastasis models in vivo. (
  • von Willebrand factor (vWF) binds the exposed collagen and binds GP Ib-IX-V complex on the surface of the platelet. (
  • A prolonged bleeding time in a patient with a normal platelet count is indicative of a qualitative platelet abnormality, von Willebrand disease (see Chap. 135), or afibrinogenemia (see Chap. 124). (
  • The major defect is in platelet adhesion due to a decrease in platelet interactions with von Willebrand factor, but abnormalities in thrombin-induced aggregation are also present. (
  • On the other hand, platelet factor 4 (PF4), β-thromboglobulin, von Willebrand factor (vWF), 11 12 and GPIbα, 13 one of the 4 subunits of the GPIb-V-IX complex with GPIbβ, GPV and GPIX, 14 appear at later, more differentiated stages. (
  • It is a receptor for fibrinogen [1] and von Willebrand factor and aids platelet activation . (
  • A Lyn - Vav - Rac1 - PI3K - Akt pathway mediates von Willebrand factor -induced activation of integrin alpha(IIb )beta(3) to promote GPIb-IX-dependent platelet activation. (
  • Glycoprotein Ib functions as a receptor for von Willebrand factor and for thrombin. (
  • Platelet endothelial cell adhesion molecule-1 inhibits platelet response to thrombin and von Willebrand factor by regulating the internalization of glycoprotein Ib via AKT/glycogen synthase kinase-3/dynamin and integrin aIIbß3. (
  • Platelet adhesion is mediated primarily by von Willebrand factor (VWF), a large multimeric protein present in both plasma and the extracellular matrix of the subendothelial vessel wall, which serves as the primary "molecular glue," providing sufficient strength to withstand the high levels of shear stress that would tend to detach them with the flow of blood. (
  • After plaque rupture, plasma von Willebrand factor (vWF) binds to collagen, and platelets adhere to immobilised vWF via GPIb-GPV-GPIX and integrin α IIb β 3 (GPIIb/IIIa). (
  • This complex is the receptor of fibrinogen, fibronectin and von Willebrand factor, and mediates platelet adhesion and aggregation. (
  • In Project 3, Dr. Ruggeri will build on advances in the structure of von Willebrand Factor (VWF) and platelet GPIb. (
  • Platelets play an important role in the primary hemostasis by interacting with sub endothelium-bound von Willebrand factor (vWf) via the platelet membrane glycoprotein lb complex. (
  • Thromboxane A2 (TXA2), produced by activated platelets, has prothrombotic properties, stimulating activation of new platelets as well as increasing platelet aggregation. (
  • Metabolic labeling of endothelium with [35S]methionine demonstrated that both GPIIb and GPIIIa were actively synthesized in culture. (
  • Using the technique of crossed immunoelectrophoresis, evidence was obtained that the endothelial cell forms of GPIIb and GPIIIa may exist complexed to one another after solubilization in Triton X-100. (
  • The disease is caused by mutations in either alpha(IIb)[glycoprotein (GP) IIb] or beta(3) (GPIIIa) genes that lead to a lack or dysfunction of the integrin alpha(IIb)beta(3) which serves as a fibrinogen receptor. (
  • CD61 (GPIIIa, ITGB3) is a glycoprotein found on megakaryocytes, platelets and their precursors. (
  • Glanzmann thrombasthenia results from abnormalities in either GPIIb or GPIIIa, resulting in loss of GPIIb/IIIa receptor function. (
  • The complex is formed via calcium-dependent association of gpIIb and gpIIIa, a required step in normal platelet aggregation and endothelial adherence. (
  • Hence, this calcium increase triggers the calcium-dependent association of gpIIb and gpIIIa to form the activated membrane receptor complex gpIIb/IIIa, which is capable of binding fibrinogen (factor I), resulting in many platelets "sticking together" as they may connect to the same strands of fibrinogen, resulting in a clot. (
  • The αIIbβ3 complex integrin is encoded by ITGA2B and ITGB3 genes (GPIIb and GPIIIa respectively). (
  • In this chapter, emphasis has been placed on the core mechanisms underlying the broad categories of hypersensitivity responses distinguished on the basis of the Gell and Coombs classification and based on differences in the immune reactants (antibodies or cells), the form of the presented antigen, and the effector mechanisms involved. (
  • Previously we have shown that monoclonal antibody (MAb) AAP2 produced in our laboratory bound to a 110-kD platelet antigen and gave an enhanced binding to activated platelet membrane. (
  • In this study we demonstrated that platelet lysate depleted of the antigen through adsorption by an AAP2-solidified affinity column was bound by MAbs against CD62 and CD42 but not by MAb 5.6E against CD31 or AAP2 on the immunoblot. (
  • To analyze directly the role of CD31 in platelet function, we produced a MAb, AAP2, which was found to recognize CD31 antigen. (
  • Cooperation between major histocompatibility complex mismatched mononuclear cells from a human chimera in the production of antigen-specific antibody. (
  • This finding is in contrast with the concept that antigen recognition by T cells is major histocompatibility complex (MHC) restricted. (
  • Tested positive against native human antigen. (
  • Immune responses in the CNS may be directed against a self or non-self antigen and can involve cellular and molecular pathways that rely on cell-cell communication. (
  • Aruffo and Seed, "Molecular cloning of a two CD7 (T-cell leukemia antigen) cDNAs by a COS cell expression system," The EMBO Journal 6:3313-3316 (1987). (
  • We have used an immunogold-surface replica technique to study the distribution of GPIIb-IIIa and bound fibrinogen over broad areas of surface membranes in unstimulated, as well as thrombin-activated and ADP-activated human platelets. (
  • On thrombin-stimulated platelets, approximately 65% of the GPIIb-IIIa molecules were in clusters within the plane of the membrane. (
  • Furthermore, the complex can be activated by thrombin. (
  • Thrombin binding to its receptor activates protein kinase C and increases the level of inositol triphosphate. (
  • Vitamin E has also been found in culture to decrease plasma production of thrombin, a protein which binds to platelets and induces aggregation. (
  • DMP754, upon its conversion with esterases to its free acid form XV459, and XV459 itself, demonstrated high potency (IC 50 = 0.030-0.060 μM) in inhibiting human platelet aggregation induced by ADP (100 μM), thrombin receptor agonist peptide (10 μM) or collagen (20 μg/ml) in citrate or heparin. (
  • Binding sites for thrombin are preserved in thrombasthenic platelets, allowing the platelets to be activated for aggregation. (
  • Abnormalities of platelet coagulant activity, that is, the ability of platelets to facilitate thrombin generation (see Chap. 111 and Chap. 112), can also lead to a hemorrhagic diathesis, but this platelet defect is unique in not usually producing mucocutaneous hemorrhage or a prolonged bleeding time. (
  • ADP, epinephrine, FITC isomer I, 3,3′-diaminobenzidine tetrahydrochloride, and a control polyclonal antibody against human C4 were purchased from Sigma Chemical Co. Collagen was obtained from Chronolog Co. Thrombin (Fibrindex) was from Ortho Diagnostics Inc. GammaBind-Plus column was purchased from Pharmacia BioTech. (
  • MAb AAP2 was produced from a hybridoma derived from BALB/c mice spleen cells after immunization with thrombin-activated human platelets and fusion with Sp2/0 Ag14 myeloma cells. (
  • Thereafter, soluble agonists, ADP, thrombin, TxA 2 , produced/released at the site of vascular injury act in autocrine and paracrine mode to amplify platelet activation and to recruit circulating platelets to the developing thrombus. (
  • In addition to activating platelets and clotting fibrinogen, thrombin activates factor XIII, which cross-links fibrin monomers. (
  • Moreover, F-NDP-Bit specifically binds to activated platelets incorporated into a clot generated by thrombin-activated rat platelet-rich plasma (PRP). (
  • Background- Thrombin is the most potent agonist of platelets and plays a critical role in the development of arterial thrombosis. (
  • Methods and Results- Platelet aggregation studies demonstrated that PAR4 activity is markedly enhanced by thrombin-PAR1 interactions. (
  • A combination of bivalirudin (hirulog) plus a novel PAR4 pepducin antagonist, P4pal-i1, effectively inhibited aggregation of human platelets to even high concentrations of thrombin and prevented occlusion of carotid arteries in guinea pigs. (
  • 1 Thrombus-bound thrombin is the primary mediator of platelet activation and aggregation, which have been shown to be heightened in the setting of angioplasty and stenting. (
  • 6 However, blockade of only PAR1 may not be sufficient to prevent acute thrombin-mediated platelet aggregation and thrombosis because of the presence of PAR4, the other thrombin receptor present on platelets. (
  • 12 To compensate for the lack of exosite I binding, PAR4 has optimized its cleavage sequence to provide high-affinity interactions with the active site and uses an anionic cluster to slow dissociation from the cationic thrombin. (
  • The cleaved PAR1 exodomain retains the Hir motif and binds to exosite I, 11 suggesting that thrombin may remain tethered to the surface of human platelets via its association with the cleaved PAR1 receptor ( Figure 1 A). (
  • PAR4-dependent platelet aggregation is inhibited upon blocking thrombin-PAR1 interactions. (
  • A, Sequential model of thrombin activation of the PAR1-PAR4 heterodimeric complex. (
  • 11 The GPIb-IX-V complex is also a key receptor in mediating platelet-dependent coagulation, particularly with respect to the intrinsic pathway of coagulation, and has binding sites within the N-terminal domain of GPIbα for high molecular weight (HMW) kininogen, Factors XI and XII and α-thrombin. (
  • We have included thrombin and fibrinogen given their importance to the platelet response but recognize many other coagulation factors not discussed are also important for cancer. (
  • In thrombin‐activated platelets, a threefold increase was found in the expression of GP IIb/IIIa over that in fresh platelets. (
  • YY-39 was found effectively to inhibit platelet aggregation induced by adenosine diphosphate (ADP), thrombin and thromboxane A2 (TXA2). (
  • The αIIbβ3 integrin and GPIb-V-IX complex identify distinct stages in the maturation of CD34+cord blood cells to megakaryocytes. (
  • The platelets arise from the fragmentation of the cytoplasm of megakaryocytes in the bone marrow and circulate in blood as disc-shaped anucleate particles for 7-10 days. (
  • The deficiency is uniformly present throughout the platelet population and is present in endothelial cells and precursor megakaryocytes. (
  • These antibodies can also react with the developing megakaryocytes in the bone marrow, leading to decreased production of platelets (ineffective thrombopoiesis). (
  • Isoform 1 and isoform 2 were identified in platelets and megakaryocytes, but not in reticulocytes or in Jurkat and U937 white blood cell line. (
  • In brief, integrin synthesis occurs in the megakaryocytes with the αIIbβ3 complex formation in the endoplasmic reticulum (ER). (
  • Indeed, a role for α IIb β 3 in platelet release from megakaryocytes has been shown. (
  • Schematic representation of the origin and development of megakaryocytes : - The pluripotential stem cell produces a progenitor cell committed to megakaryocyte differentiation (Meg-CFC) which undergoes mitosis. (
  • Upon completion of endomitosis, the immature progenitor cells become large, morphologically identifiable mature megakaryocytes  MEGAKARYOCYTE now sheds the platelets. (
  • Platelets are produced by the fragmentation of megakaryocytes in the bone marrow. (
  • CD61 is expressed by activated T cells, granulocytes, and platelet. (
  • CD61 is found along with the alpha IIb chain in platelets. (
  • Like other integrins, CD61 is known to participate in cell adhesion as well as cell-surface mediated signaling. (
  • Diseases associated with CD61 dysfunction include Glanzmann Thrombasthenia and Platelet type-16 Bleeding Disorder. (
  • HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Transfer of tissue factor from leukocytes to platelets is mediated by CD15 and tissue factor Ursula Rauch, Diana Bonderman, Bernd Bohrmann, Juan J. Badimon, Jacques Himber, Markus A. Riederer, and Yale Nemerson We describe thrombogenic tissue factor (TF) on leukocyte-derived microparticles and their incorporation into spontaneous human thrombi. (
  • Polymorphonuclear leukocytes and monocytes transfer TF1 particles to platelets, thereby making them capable of triggering and propagating thrombosis. (
  • Both the inhibition of TF transfer to platelets by antagonizing the interaction CD15 with P-selectin and the direct interaction of TF itself suggest a novel therapeutic approach to prevent thrombosis. (
  • Our data suggest that monocytes and possibly PMN leukocytes are the source of circulating TF which is transferred to platelets, thereby making F platelets capable of triggering and propagating thrombosis. (
  • Factors that stimulate thrombosis include vascular damage, stimulation of platelets and activation of the coagulation cascade. (
  • Under normal circumstances, the resistance of the endothelial cell lining to interactions with platelets and coagulation factors prevents thrombosis. (
  • Platelets primarily mediate hemostasis and thrombosis, whereas leukocytes are responsible for immune responses. (
  • Since platelets interact with leukocytes at the site of vascular injury, thrombosis and vascular inflammation are closely intertwined and occur consecutively. (
  • Recent studies using real-time imaging technology demonstrated that platelet-neutrophil interactions on the activated endothelium are an important determinant of microvascular occlusion during thromboinflammatory disease in which inflammation is coupled to thrombosis. (
  • Over the recent years, it has been well established that interactions between CD40 and its immunomodulating ligand (CD40L), expressed in a variety of cell types including platelets, vascular wall cells, and immune cells, are actively involved in atherogenetic and thrombotic mechanisms and may serve as a link between inflammation, atherosclerosis, and thrombosis ( 2 ). (
  • Thrombosis plays a critical role in the pathogenesis of ACS, as disruption of an atherosclerotic plaque exposes flowing blood to sub-endothelial collagen, tissue factor, and other pro-coagulant molecules that trigger activation of platelets and formation of fibrin within the vessel lumen. (
  • Patients with renal diseases are prone to both thrombosis and bleeding, as they have profound changes in all three classic components of coagulation, defined approximately 150 years ago by Virchow: blood flow, vessel wall (endothelial injury), and coagulation properties of the blood (e.g., coagulation and fibrinolytic systems and platelets). (
  • These studies suggest that targeting the PAR1-PAR4 complex may present a novel therapeutic opportunity to prevent arterial thrombosis. (
  • Altogether, this interdisciplinary program will enable remarkable synergies amongst a group of accomplished investigators who will test new hypotheses and utilize and develop cutting edge methodologies to advance understanding of cell adhesion events in vascular biology and thrombosis. (
  • The GPIb-IX-V complex is a pivotal receptor complex in hemostasis and thrombosis. (
  • In addition to its primary role in binding VWF, this N-terminal domain of GPIbα is a major binding site for multiple ligands mediating platelet interactions with matrix and other cell types in thrombosis and inflammation ( Figure 1 ). (
  • 10 These two interactions are fundamental to crosstalk between platelets and leukocytes, including those involving platelet-and leukocyte-derived microparticles, in both thrombosis and the co-associated inflammatory response. (
  • Numerous studies now indicate that microparticles have biological activities and may be involved in thrombosis, cell inflammation, angiogenesis and cell-to-cell communication ( 5 - 12 ). (
  • Platelet dysfunction contributes to a wide range of obvious pathologic conditions, such as bleeding or thrombosis, but normal platelet function is also linked to diseases not immediately associated with hemostasis or thrombosis, such as cancer.Since the description of Trousseau's syndrome in 1865 various experimental and clinical evidences have detailed the interaction of platelets with primary tumors and circulating metastatic tumor cells. (
  • Under normal circumstances, the endothelial cells lining the blood vessels resist the interactions with platelets and coagulation factors and therefore thrombosis doesn't occur. (
  • One of them (YY-39) was tested for its effects on platelets and thrombosis in vivo. (
  • Western-blot analysis showed that the endothelial cell analogues were similar in size to their platelet counterparts, and were present in cells that had been in culture for over 2 mo. (
  • Immunohistochemistry for endothelial cell markers including vWF, CD31, CD34 and endothelial nitric oxide synthase (eNOS) and platelet glycoprotein Ib/IX or IIb/IIIa was performed and semiquantitatively graded. (
  • Abstract CD31/platelet endothelial cell adhesion molecule 1 (PECAM-1) is expressed on platelets, endothelial cells, myeloid cells, monocytes, and certain lymphocyte subsets. (
  • This step leads to rapid platelet aggregation which physically plugs ruptured endothelial cell surface. (
  • anticoagulant endothelial cell factors. (
  • Activated platelets undergo the release reaction, during which they secrete contents that further promote aggregation and inhibit the naturally anticoagulant endothelial cell factors. (
  • To take advantage of known physiological drivers of thrombopoiesis, we have developed a microfluidic human platelet bioreactor that recapitulates bone marrow stiffness, extracellular matrix composition, micro-channel size, hemodynamic vascular shear stress, and endothelial cell contacts, and it supports high-resolution live-cell microscopy and quantification of platelet production. (
  • Platelet adhesion/thrombus formation in the endocardium was found in limited sites in which the overlying endothelium was deficient in eNOS and CD34. (
  • When warfarin-treated cases were excluded, there was a significant correlation between the immunohistochemical grade for vWF and the degree of platelet adhesion/thrombus formation in the endocardium. (
  • When platelet activation is initiated, a conformational change in the integrin to a high-affinity state for the plasma protein fibrinogen results in platelet aggregation and, finally, thrombus formation. (
  • In Project 1, Dr. Ginsberg will study the activation of integrins and resulting thrombus formation by platelets and arrest of leukocytes. (
  • Inhibitors of this interaction are useful in modulating platelet thrombus formation. (
  • Low platelet concentration is called thrombocytopenia , and is due to either decreased production or increased destruction . (
  • Both quantitative and qualitative platelet abnormalities can produce these symptoms, so it is necessary to exclude thrombocytopenia by performing a platelet count (see Chap. 117). (
  • Loss of the platelet GPIb/IX/V complex due to abnormalities in GPIba, GPIbb, or GPIX results in the Bernard-Soulier syndrome, which is characterized by giant platelets and thrombocytopenia. (
  • A reduced platelet count occurs in patients with purely quantitative platelet disorders (inherited or acquired) as well as in patients who have inherited qualitative platelet disorders associated with thrombocytopenia. (
  • 3,7,8 One of the consequences of this conformational change is the exposure of ligand-induced binding sites (LIBSs) and patients with preformed antibodies against LIBSs can develop GPIIb/IIIa-induced thrombocytopenia. (
  • Present only with thrombocytopenia, and due to difficulty in detecting platelet Ab diagnosis is typically made by exclusion. (
  • Design and Methods We describe two Italian families with moderate thrombocytopenia with large platelets, defective platelet function and moderate/severe mucocutaneous bleeding, transmitted as an autosomal dominant trait and associated with a novel integrin β 3 -gene ( ITGB3 ) mutation. (
  • Note that even in EDTA blood pseudo-thrombocytopenia recovers 3 days after the bolus as abciximab effect on GP Iib/IIIA wears off). (
  • Bernard-Soulier syndrome (BSS) is an inherited, usually autosomal recessive, platelet bleeding abnormality, characterized by a prolonged bleeding time, large platelets and thrombocytopenia. (
  • 1 For the homeostasis of the vasculature it is crucial to maintain a normal platelet count in the blood.Experimental thrombocytopenia in mice inducedby neuraminidase/anti-platelet serum resulted in a 50% reduction in experimental metastasis and this could be reversed by transfusion of platelet-rich plasma transfusion. (
  • Platelet disorders can be either a decrease in number of platelets (thrombocytopenia) or defect in platelet function. (
  • Following activation integrin alpha-IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. (
  • CHO-Anti-Human Integrin alpha 2b beta 3 MAb stable cell line is clonally-derived from a CHO cell line, which has been transfected with an anti-human Integrin alpha 2b beta 3 MAb gene to allow expression of the MAb. (
  • 2-6 Major consequences of signal transduction following engagement of GPVI or GPIb-IX-V include (1) activation of platelet integrins, primarily α IIb β 3 that binds vWF or fibrinogen and mediates platelet aggregation, and (2) activation of pathways leading to metalloproteinase-dependent receptor ectodomain shedding. (
  • In addition to adhesion, integrins are known to participate in cell-surface mediated signalling. (
  • In this report, we demonstrate that the cellular entry of HFRS-associated hantaviruses is facilitated by specific integrins expressed on platelets, endothelial cells, and macrophages. (
  • Infection of human umbilical vein endothelial cells and Vero E6 cells by the HFRS-causing hantaviruses Hantaan (HTN), Seoul (SEO), and Puumala (PUU) is inhibited by antibodies to α v β 3 integrins and by the integrin ligand vitronectin. (
  • The cellular entry of HTN, SEO, and PUU viruses, but not the nonpathogenic Prospect Hill (PH) hantavirus (i.e., a virus with no associated human disease), was also mediated by introducting recombinant α IIb β 3 or α v β 3 integrins into β 3 -integrin-deficient CHO cells. (
  • These findings indicate that pathogenic HPS- and HFRS-causing hantaviruses enter cells via β 3 integrins, which are present on the surfaces of platelets, endothelial cells, and macrophages. (
  • Since β 3 integrins regulate vascular permeability and platelet function, these findings also correlate β 3 integrin usage with common elements of hantavirus pathogenesis. (
  • Interaction of integrins ?v?3 and glycoprotein IIb-IIIa with fibrinogen. (
  • Specific studies will address the activation of integrins in purified systems, the role of RIAM, the interactions and structure of integrin transmembrane domains, and the in vivo and ex vivo consequences of perturbing integrin activation in platelets and leukocytes. (
  • Most integrins bind to extracellular matrix (ECM) molecules, and they transmit signals that are critical in growth, development, tissue homeostasis, and host defense. (
  • Hence, the exterior and interior of a cell are physically linked by integrins, which allows the bidirectional transmission of mechanical and biochemical signals across the plasma membrane, and leads to a cooperative regulation of cellular functions, including adhesion, migration, growth, survival, and differentiation. (
  • Most integrins bind to ECM components. (
  • Low-dose, long-term aspirin use irreversibly blocks the formation of thromboxane A2 in platelets, producing an inhibitory effect on platelet aggregation. (
  • MAb 5.6E did not have any effect on platelet aggregation. (
  • The binding between GPIbα and vWF mediates the capture of platelets to the injured vascular wall. (
  • A cascade of biochemical events propagates and matures the inflammatory response, involving the local vascular system, the immune system, and various cells within the injured tissue. (
  • Vitamin E's antithrombotic and anticoagulant activities involves the downregulation of the expression of intracellular cell adhesion molecule(ICAM)-1 and vascular cell adhesion molecule(VCAM)-1 which lowers the adhesion of blood components to the endothelium. (
  • Human platelets participate in a number of adhesive interactions, including binding to exposed subendothelium after vascular injury, and platelet-platelet cohesion to form large aggregates. (
  • A number of agonists, generated at the interface between the vessel wall and circulating blood at the site of vascular injury, have been shown to activate platelets. (
  • A variety of drugs that inhibit platelet function have been shown to decrease morbid events in patients with established cardiovascular atherosclerotic diseases, as evidenced by stroke or transient ischemic attacks, myocardial infarction, unstable angina or the need for vascular bypass or angioplasty. (
  • Hantaviruses replicate primarily in the vascular endothelium and cause two human diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). (
  • Recent intravital microscopic studies have provided compelling evidence that activated neutrophils adherent to inflamed ECs can support homotypic and heterotypic cell-cell interactions and that platelet-neutrophil aggregation on activated ECs is the crucial determinant of microvascular occlusion during vascular inflammation ( Fig. 1 ) [ 8 , 9 ]. (
  • Heterotypic cell-cell interactions during vascular inflammation. (
  • Tissue and vascular injuries activate ECs, resulting in not only the expression of adhesion molecules including P-and E-selectins, ICAMs, and vascular cell adhesion mole-cule-1 (VCAM-1) but also the production and release of vWF, reactive oxygen species (ROS), and inflammatory cytokines [ 3 , 17 - 19 ]. (
  • Formation of vascular blood clots is also a leading cause of death in cancer patients because cancer cells create conditions that favor clotting. (
  • Platelet membrane glycoprotein complex essential for normal platelet adhesion and clot formation at sites of vascular injury. (
  • On vascular injury, platelets adhere to the site of injury, usually the denuded vascular intimal surface. (
  • Because the surface of each platelet has about 50,000 Gp IIb/IIIa-binding sites, numerous activated platelets recruited to the site of vascular injury can rapidly form an occlusive aggregate by means of a dense network of intercellular fibrinogen bridges. (
  • They are expressed in a variety of tissues such as the immune system (in both B and T cells), the vascular wall, and activated platelets. (
  • Support is requested to continue a program designed to advance understanding of molecular mechanisms of vascular disease and to promote development of new diagnostic, therapeutic, and preventive strategies through the collaborative efforts of a group of experienced scientists focused oh the unifying theme of cell adhesion. (
  • Vascular Cell Adhesion Molecule-1 Mediates Lymphocyte Adherence to Cytokine-Activated Cultured human Endothelial Cells," Blood 76:965-970 (1990). (
  • MVs from vascular and resident cells by facilitating exchange of biological information between neighboring cells serve as cellular effectors in the bloodstream and play a key role in all stages of disease progression. (
  • MV contribution to vascular remodeling is also discussed, with a particular emphasis on the effect of MVs on the crosstalk between endothelial cells and smooth muscle cells, and their role regulating the active process of AT-driven angiogenesis and neovascularization. (
  • Activation of this complex initiates the platelet aggregation and the formation of primary platelet plug, a fibrin clot. (
  • [6] Formation of this platelet plug (primary hemostasis) is associated with activation of the coagulation cascade with resultant fibrin deposition and linking (secondary hemostasis). (
  • These processes may overlap: the spectrum is from a predominantly platelet plug, or "white clot" to a predominantly fibrin, or "red clot" or the more typical mixture. (
  • The initial hemostatic plug, composed primarily of platelets, is stabilized further by a fibrin mesh generated in secondary hemostasis. (
  • he drug specifically and irreversibly inhibits the P2Y12 subtype of ADP receptor, which is important in aggregation of platelets and cross-linking by the protein fibrin. (
  • It is an important part of hemostasis (the cessation of blood loss from a damaged vessel), wherein a damaged blood vessel wall is covered by a platelet and fibrin -containing clot to stop bleeding and begin repair of the damaged vessel. (
  • The platelet plug is anchored and stabilized by the developing fibrin mesh. (
  • However, if platelets and fibrin amass in sufficient quantity to obstruct coronary blood flow, symptoms of ischaemia ensue. (
  • It participates in platelet aggregation and fibrin formation in the blood clotting mechanism. (
  • It is also known that another large glycoprotein named fibronectin, which is a major extracellular matrix protein, interacts with fibrinogen and fibrin, and with other structural molecules such as actin, collagen and proteoglycans. (
  • This transmembrane glycoprotein complex is composed of four subunits: GPIbα, GPIbβ, GPV and GPIX. (
  • GPIbα and GPIbβ are linked by disulfide bridges, while the GPV and GPIX associate non-covalently with the complex. (
  • Platelet glycoprotein Ibα (GPIbα) extracellular domain, which is part of the receptor complex GPIb-IX-V, plays an important role in tumor metastasis. (
  • To validate our findings, we further obtained mouse anti-human GPIbα monoclonal antibody YQ3 through the same approach. (
  • The GPIb-IX-V complex consists of four subunits: GPIbα, GPIbβ, GPIX, and GPV. (
  • GPIbα is the largest and most important component of the complex. (
  • This study defined the progressive expression of the GPIb-V-IX complex during in vitro MK maturation and compared it to that of GPIIb, an early MK marker. (
  • GPIb-V-IX expression appeared at day 3 of culture and was strictly dependent on MK cytokine induction, whereas GPIIb was already present in immature CD34 + cells. (
  • Microscopy studies confirmed the late appearance of GPV, which was principally localized in the cytoplasm when GPIb-IX was found on the cell surface, suggesting a delayed program of GPV synthesis and trafficking. (
  • This study shows that the subunits of the GPIb-V-IX complex represent unique surface markers of MK maturation. (
  • The genes coding for GPIb-IX and GPV are useful tools to study megakaryocytopoiesis and for tissue-specific or conditional expression in mature MK and platelets. (
  • GPIbbeta missense mutations from Bernard-Soulier syndrome were examined for changes to GPIb-IX complex surface expression. (
  • The heterotypic platelet-neutrophil interactions are mainly mediated by binding of neutrophil P-selectin glycoprotein ligand-1 (PSGL-1) and αMβ2 integrin to platelet P-selectin and glycoprotein Ibα (GPIbα), respectively [ 8 - 12 ]. (
  • Platelet Glycoprotein GPIb-IX Complex" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (
  • Congenital deficiency of the GPIb-IX complex results in Bernard-Soulier syndrome. (
  • The platelet glycoprotein GPV associates with GPIb-IX and is also absent in Bernard-Soulier syndrome. (
  • This graph shows the total number of publications written about "Platelet Glycoprotein GPIb-IX Complex" by people in this website by year, and whether "Platelet Glycoprotein GPIb-IX Complex" was a major or minor topic of these publications. (
  • Below are the most recent publications written about "Platelet Glycoprotein GPIb-IX Complex" by people in Profiles. (
  • 7 The GPIb-IX-V complex consists of four subunits, GPIbα disulphide-linked to two GPIbαβ subunits, GPIX and GPV in a ratio of 2:4:2:1, respectively ( Figure 1 ). (
  • GPIbα also contains a mucin-like domain elevating the major ligand-binding domain located within the N-terminal 282 residues. (
  • The GPIb-IX-V complex composed of GPIbα disulphide-linked to two GPIbβ subunits, and noncovalently associated with GPIX and GPV. (
  • The GPIb-IX-V also plays a role in maintaining platelet shape by linking the platelet surface to a sub-membranous network of actin filaments, the platelet membrane skeleton. (
  • 6 , 12 Binding of VWF to the GPIb-IX-V complex initiates a signaling cascade leading to activation of the platelet integrin, α IIb β 3 (GPIIb-IIIa), and platelet aggregation. (
  • It is an important collagen receptor involved in collagen-induced platelet activation and adhesion. (
  • The interaction with collagen leads to stabilization of the platelets. (
  • In particular, a focus on proteolytic regulation of the platelet collagen receptor, glycoprotein (GP)VI, illustrates many of the key biochemical, cellular, and clinical implications of current research in this area. (
  • Endothelial disruption exposes subendothelial collagen, which activates platelets by binding glycoprotein VI (GPVI) and integrin α 2 β 1 on the platelet surface. (
  • Furthermore, YY-39 blocked platelet adhesion to soluble collagen and bound to purified GPIIb/IIIa in a dose-dependent manner. (
  • Interactive sites for important ligands of VWF (such as factor VIII, collagen, glycoprotein Ibα, integrin αIIbβ3 and protease ADAMTS13) have been identified, and mutagenesis studies have confirmed the physiological relevance of the interactions between VWF and these ligands. (
  • RGD tripeptides, which are required for many integrin-ligand interactions, are absent from all hantavirus G1 and G2 surface glycoproteins, and GRGDSP peptides did not inhibit hantavirus infectivity. (
  • No. 4,683,291, inhibition of platelet function is disclosed with synthetic peptides designed to be high affinity antagonists of fibrinogen binding to platelets. (
  • Other synthetic peptides and their use as inhibitors of fibrinogen binding to platelets are disclosed by Koczewiak et al. (
  • Combined with their prevalence in ticks and platelet inhibitory functions, this family of peptides might be conserved tick anti-haemostatic molecules. (
  • Antiinflammatory Peptides (Antiflammins) Inhibit Synthesis of Platelet-Activating Factor, Neutrophil Aggregation and Chemotaxis, and Intradermal Inflammatory Reactions", J. Exp. (
  • In the resting state the contact between the two protein subunits (necessary for the complex activation) is prevented by aggregin, which disables their contact necessary for the complex activation. (
  • Determination of a cAMP-dependent protein kinase phosphorylation site in the C-terminal region of human endothelial actin-binding protein. (
  • The actin-binding protein profilin was isolated from Tetrahymena thermophila by affinity chromatography, and the peptide sequence was determined for part of the protein. (
  • Allergic reactions to drugs are not always the result of the drug's protein-binding capacity, biotransformation, or degradation. (
  • From the time of the early immunochemical studies on antigenicity and haptens, organic chemicals of small molecular mass have been assumed to be antigenic and capable of stimulating an immune response only as a complex with a macromolecular carrier, usually protein. (
  • GPIIb/IIIa is the major membrane receptor protein that is key to the role of the platelet aggregation response. (
  • GPIIb is the alpha-subunit of this platelet membrane protein. (
  • Alpha-tocopherol downregulates GPIIb promoter activity which results in reduction of GPIIb protein expression and decreased platelet aggregation. (
  • The gene segments L, S, and M encode the viral RNA polymerase, the nucleocapsid protein (N), and two integral membrane surface glycoproteins (G1 and G2), respectively. (
  • During clot formation, integrin αIIbβ3 binds to a protein called fibrinogen. (
  • Attachment of integrin αIIbβ3 from adjacent platelets to the same fibrinogen protein helps platelets cluster together (platelet cohesion) to form a blood clot. (
  • This abnormally active protein is unable to reach the surface of the platelet where it is needed to bind to other platelets during clot formation. (
  • The CD40 ligand (CD40L) protein is a type II membrane protein with an intracellular amino terminus and an external carboxy terminus. (
  • in all mammals , coagulation involves both a cellular (platelet) and a protein (coagulation factor) component. (
  • The primary activator of the blood coagulation system is tissue factor (TF), a cell-membrane-anchored protein that is abundant in the adventitia of normal blood vessels and the intima and media of atherosclerotic arteries. (
  • Analytical sodium dodecyl sulfate-polyacrylamide gel electrophoresis of human spinal cord components followed by immunoblots with sera under study revealed that the serum antibody was specific for the high molecular weight protein subunit of neurofilaments. (
  • The pathogenesis of diabetic retinopathy is complex and has involved multiple pathways including accumulation of polyol compounds and advanced glycation end products, increased oxidation stress and activation of the protein kinase C pathway, production of growth factors, and inflammation ( 1 ). (
  • A functional integrin is a heterodimeric protein complex consisting of an α and a β subunit. (
  • High affinity binding of many protein ligands, including Fg, to α M β 2 involves a segment of ∼200 amino acids in the α M subunit, termed the I (or A) domain ( 23 )( 26 )( 27 ). (
  • The MoAbs included antibodies against the platelet glycoprotein (GP) IIb/IIIa complex and against two activation‐dependent antigens, one of which was a component of the internal platelet alpha‐granule membrane (GMP 140) and the other of which was a 53‐kD protein derived from platelet lysosomes. (
  • Storage of platelet concentrates for 5 days resulted in a 60 percent increase in GP IIb/IIIa expression compared to Day 0 and increased binding of the MoAbs directed against GMP‐140 from 3 to 16 percent and against the 53‐kD protein from 2 to 8 percent of the platelets, respectively. (
  • When the blood vessel wall is damaged, platelet membrane glycoproteins interact with the extracellular matrix. (
  • Its main function is in the adhesion of cells to the extracellular matrix components. (
  • and vessel wall extracellular matrix constituents that come in contact with adherent platelets (e.g. (
  • Key components of the plaque include a fibrous cap, composed of smooth muscle cells and fibroblasts, an overlying layer of endothelial cells, and an internal core that contains cholesterol and other lipids, macrophages, foam cells (which are derived from macrophages), other inflammatory cells, and extracellular matrix. (
  • therefore, there is a balance shift toward inhibition of vasoconstriction and platelet aggregation. (
  • PKC plays a role in smooth muscle cell proliferation, and, thus, the inhibition of PKC results in inhibition of smooth muscle cell proliferation, which is involved in atherogenesis. (
  • Some would add the subsequent retraction and platelet inhibition as fourth and fifth steps to the completion of the process [7] and still others a sixth step wound repair . (
  • Maximal platelet aggregation inhibition was achieved at 50 to ≥80% receptor occupancy, depending on the agonist used. (
  • It is proposed that the inhibition involves a defect in the mobilization from the storage sites of the platelet granules to the outer membrane. (
  • 1,2 Because this GPIIb/IIIa activation represents the final common pathway of all types of platelet activation mechanisms, GPIIb/IIIa represents an ideal therapeutic target for effective platelet inhibition. (
  • 5 Chronic stimulation of PAR1 on endothelium, smooth muscle cells, and other mesenchymal cells leads to inflammation and intimal hyperplasia, whereas inhibition of PAR1 attenuates restenosis in animal models. (
  • This invention relates to compounds having the following formula ##STR1## or a pharmaceutically acceptable salt which are useful in the inhibition of platelet aggregation. (
  • The frequency of circulating TFH cells in both the patients and HC was analyzed by flow cytometry. (
  • Rabbit antibodies against CD31 completely inhibited the binding of AAP2 to platelets in the flow cytometry analysis. (
  • In contrast to clinically used GPIIb/IIIa blockers, which are all conformation unspecific, activation-specific GPIIb/IIIa blockers do not induce conformational changes in GPIIb/IIIa or outside-in signaling, as evaluated by ligand-induced binding-site (LIBS) exposure in flow cytometry or P-selectin expression in immunofluorescence microscopy, respectively. (
  • Shattil SJ, Cunningham M, Hoxie JA: Detection of activated platelets in whole blood using activation-dependent monoclonal antibodies and flow cytometry. (
  • Detection of platelet activation with monoclonal antibodies and flow cytometry. (
  • The binding of MoAbs to platelets fixed with 1 percent paraformaldehyde was measured by flow cytometry. (
  • Platelet membrane glycoproteins (GP) IIb and IIIa constitute a receptor for fibrinogen that, together with fibrinogen and calcium, is largely responsible for mediating the formation of the primary hemostatic plug. (
  • As the glycoprotein GPIIb/IIIa complex is the major receptor for fibrinogen, its impaired activation prevents fibrinogen binding to platelets and inhibits platelet aggregation. (
  • GPIIb-IIIa (integrin α IIb β 3 ), the platelet receptor for fibrinogen and vWF, is a well-studied example of an early MK marker. (
  • Mechanisms, to the extent that they are currently understood, of other types of "hypersensitivity" reactions or intolerances, some mediated by antibodies other than IgE, and others by cells, are also discussed. (
  • Using highly specific polyclonal and monoclonal antibodies as probes, we could detect the presence of both of these glycoproteins in cultured human umbilical vein endothelial cells. (
  • Idiopathic thrombocytopenic purpura (ITP) is a primary autoimmune disease with a decreased platelet count caused by platelet destruction mediated mainly by platelet antibodies. (
  • Serum interleukin (IL)-21 and IL-6 levels were measured using ELISA, and platelet antibodies were tested using a solid phase technique. (
  • However, little is known about how B cells produce specific auto-antibodies that are activated in patients with ITP and which T cell type could induce B cells to produce antibodies in ITP patients. (
  • Platelets with antibodies on their surface are trapped in the spleen, where they are efficiently removed by splenic macrophages. (
  • These antibodies may be directed toward viral antigens and then cross-react with platelet antigens. (
  • Immunoglobulin allotype determination showed that antibodies were synthetized by host B cells. (
  • Cells were incubated with an excess of purified unconjugated CD41a (REA386) antibody followed by staining with fluorochrome-conjugated antibodies of other known clones against the same marker. (
  • Mutagenesis studies and computer modeling indicate that exclusive binding of activation-specific scFv is mediated by RXD motifs in the heavy-chain complementary-determining region (CDR) 3 of the antibodies, which in comparison with other antibodies forms an exceptionally extended loop. (
  • In conclusion, activation-specific GPIIb/IIIa blockade via human single-chain antibodies represents a promising novel strategy for antiplatelet therapy. (
  • Abcam is leading the way with our range of recombinant antibodies, knockout-validated antibodies and knockout cell lines, all of which support improved reproducibility. (
  • The ligands, denoted by letter L, signal for platelets (P) to migrate towards the wound (Site A). As more platelets gather around the opening, they produce more ligands to amplify the response. (
  • Binding of α IIb β 3 to its ligands, mainly fibrinogen, supports processes such as clot retraction and platelet aggregation. (
  • Ligands activate integrin ?IIb/?3 (platelet GPIIb-IIIa). (
  • Other adhesive ligands include P-selectin, 9 which is surface expressed on activated platelets and activated endothelial cells, and the leukocyte integrin, α M β 2 (also termed Mac-1 or CD11b/CD18). (
  • In this MIDAS motif, five noncontiguous amino acids, including the D(140), S(142), S(144), T(209), and D(242) (numbering refers to the amino acid positions in the mature α M subunit sequence), provide coordination sites for a divalent cation and ligands bind in close proximity to this motif ( 29 )( 30 ). (
  • Optimal recognition of many of the α M I domain ligands can be influenced by the activation of the α M β 2 -bearing cell, which alters receptor avidity/affinity ( 23 )( 24 )( 31 ). (
  • J. C. Loftus, T. E. O'Toole, E. F. Plow, and M. H. Ginsberg, Identification of a GPIIa-IIIa mutation in a glanzmanns variant associated with loss of RGD binding function, Blood , 74 (suppl 1) , 58a (abstract) (1989). (
  • S. E. D'Souza, M. H. Ginsberg, and E. F. Plow, Defining the ligand recognition site within the platelet adhesion receptor GPIIb-IIIa, Blood , 74 (suppl 1) , 90a (abstract) (1989). (
  • The transfer of TF1 leukocytederived particles is dependent on the interaction of CD15 and TF with platelets. (
  • This initial interaction (platelet adhesion) sets the stage for other adhesive reactions that allow the platelets to interact with each other to form an aggregate (see image below). (
  • Using it to study its interaction with platelets, we found that AAP2 had increased binding to activated platelets and inhibited platelet aggregation induced by agonists. (
  • A comparison of the receptor-mediated interaction of malondialdehyde-low density lipoprotein and maleyl-albumin has been examined in human monocytes during differentiation in vitro. (
  • Most of the knowledge related to the interaction of S. aureus with its host cells has been described in professional phagocytic cells such as macrophages. (
  • The N-terminal portion of the a and p subunits associate to form the headpiece, which contains the ligand-binding site, whereas the C -terminal segments traverse the plasma membrane and mediate interaction of the integrin with the cytoskeleton and other signaling molecules. (
  • Platelet-to-platelet interaction (platelet aggregation) is mediated by the platelet glycoprotein (GPIIb/IIIA) complex on the surface of platelet membranes. (
  • The addition of fibrinogen caused the GPIIb-IIIa molecules to cluster on the cell surface. (
  • Fibrinogen molecules then interconnect the platelets, serving as the basis for platelet aggregation. (
  • Cell-to-cell communication molecules such as cytokines play an extremely important role in mediating the process of inflammation. (
  • This study demonstrated TFH cells and effector molecules might play an important role in the pathogenesis of ITP, which are possible therapeutic targets in ITP patients. (
  • Because cells require input from their surroundings-in the form of hydrated ions, small polar molecules, large biomolecules and even other cells-they have developed strategies for overcoming this barrier. (
  • It was reported that several EC surface molecules, including platelet-EC adhesion molecule-1 (PECAM-1), CD99, EC-selective adhesion molecule (ESAM), and junctional adhesion molecules (JAMs), control this process [ 3 - 7 ]. (
  • In addition, the ECM functions as a physical barrier to or as a selective filter for soluble molecules (e.g., glomerular basement membrane). (
  • Fibrinogen sites recognized by glycoprotein IIb / IIIa complex: dodecapeptide located in the C-terminal of the fibrinogen γ chain (the most important) RGD sequence of the α chain → the Arginine-Glycine-Aspartate amino acid sequence This complex also binds vWF, fibronectin and vitronectin. (
  • The platelet integrin GP IIb-IIIa (also referred to as α IIb-β) is a calcium-dependent heterodimer complex that can bind fibronectin, fibrinogen, vWF, and vitronectin. (
  • Alpha chain 2b undergoes post-translational cleavage to yield disulfide-linked light and heavy chains that join with beta 3 to form a fibronectin receptor expressed in platelets that plays a crucial role in coagulation. (
  • Various relatively large polypeptide fragments in the cell-binding domain of fibronectin have been found to have cell-attachment activity. (
  • A new murine monoclonal antibody reports an activation-dependent change in the conformation and/or microenvironment of the platelet glycoprotein IIb/IIIa complex. (
  • Monoclonal antibody binds to integrin alphaIIb beta 3, acts on the cardiovascular system. (
  • This activation was associated with exposure of the activation-dependent epitope recognized by monoclonal antibody 7E3 and was observed also with human neutrophils. (
  • Thromboxane synthesis inhibitors, in turn, can be classified regarding which step in the synthesis they inhibit: The widely used drug aspirin acts by inhibiting the ability of the COX enzyme to synthesize the precursors of thromboxane within platelets. (
  • Glycoprotein IIb/IIIa inhibitors can be used to prevent blood clots in an effort to decrease the risk of heart attack or stroke . (
  • Of particular interest is a class of phenyl amidine derivatives useful as inhibitors of platelet aggregation. (
  • No. 4,857,508 discloses tetrapeptides having utility as inhibitors of platelet aggregation. (
  • Several platelet aggregation inhibitors have been identified from ticks. (
  • Platelet aggregation requires the binding of fibrinogen to its receptor, a heterodimer consisting of the plasma-membrane glycoproteins (GP) IIb and IIIa. (
  • The plasma membrane defines the inside and outside of the cell. (
  • In some cases, the bound ligand is released intracellularly and the receptor is then recycled to the plasma membrane. (
  • Properties and physiologic roles of the plasma membrane sodium-hydrogen exchanger. (
  • Microvesicles (MVs), small extracellular plasma membrane particles shed by activated and apoptotic cells have been widely linked to the development of CVD. (
  • Moreover, the frequencies of circulating CXCR5 + CD4 + TFH cells with inducible costimulator (ICOS) high or programmed death-1 (PD-1) high expression were notably higher in ITP with platelet-antibody-positive ( ITP (+) ) patients than in ITP with platelet-antibody-negative ( ITP (-) ) patients and HC, as were the serum IL-21 and IL-6 levels (significant). (
  • Platelet autoantibodies to specific membrane glycoproteins mediate platelet destruction and are a major agent in the pathogenetic mechanism of ITP that includes antibody-mediated cell-mediated platelet destruction and the suppression of megakaryopoiesis [ 4 - 6 ]. (
  • Applications Tested: The 2C9.G3 antibody has been tested by flow cytometric analysis of mouse splenocytes and bone marrow cells. (
  • A test is defined as the amount (µg) of antibody that will stain a cell sample in a final volume of 100 µL. (
  • 10 Rosenblum et al 11,12 also found that anti-CD31 antibody delays platelet adhesion/aggregation at sites of endothelial injury in mouse cerebral arterioles. (
  • To define the mechanism responsible for this in vivo antibody response, antibody production by peripheral blood mononuclear cells from the patient was tested in vitro after in vivo booster. (
  • Fc OxyBURST Green assay reagent comprises bovine serum albumin (BSA) that has been covalently linked to dichlorodihydrofluorescein (H 2 DCF) and then complexed with a purified rabbit polyclonal anti-BSA antibody ( A11133 ). (
  • Dichlorodihydrofluorescein (H 2 DCF) is covalently attached to bovine serum albumin (BSA), then complexed with a rabbit polyclonal anti-BSA antibody ( A11133 ). (
  • The antibody is suited for staining of formaldehyde-fixed cells. (
  • We used phage display of single-chain antibody (scFv) libraries in combination with several rounds of depletion/selection to obtain human scFvs that bind specifically to the activated conformation of GPIIb/IIIa. (
  • Human PAR1 or murine PAR4 stimulation activates αIIbβ3, which was measured with antibody PAC-1, indicating complete pathway reconstitution. (
  • e alone.8,9 Taken together, these data suggest that leukocytes are a potential source of TF microparticles that adhere to platelets within a thrombus. (
  • Platelets adhere to sites of endothelial injury and then activate, aggregate, and secrete various chemicals designed to promote further platelet recruitment and aggregation. (
  • Cerebral malaria is a form of human malaria wherein Plasmodium falciparum -infected red blood cells adhere to the blood capillaries in the brain, potentially leading to coma and death. (
  • while the 293T-αⅡbβ3Δ754 cells and 293T-αⅡbβ3Δ759 cells failed to adhere or spread on immobilized fibrinogen. (
  • Uncleaved ULVWF multimeric strings anchored to endothelial cells, or present as soluble ULVWF forms in plasma, are hyper-adhesive to platelets. (
  • ULVWF strings or soluble ULVWF forms with adherent/aggregated platelets occlude the microvasculature (arterioles and capillaries). (
  • Expression of a soluble and functional form of the human .beta.2 integrin CD11b/CD18", Proc. (
  • Prostacyclin is a vasodilating factor and inhibitor of platelet aggregation and platelet release. (
  • Platelet disorders lead to defects in primary hemostasis and produce signs and symptoms different from coagulation factor deficiencies (disorders of secondary hemostasis). (
  • Immunoreactive vWF in the endocardial endothelium was increased in overloaded human atrial appendage, which may be a local predisposing factor for intraatrial thrombogenesis. (
  • Large platelets that lack purple granules are observed in the gray platelet syndrome (a-storage pool deficiency), but one needs to be certain that the stain is working properly and that there is no plasma factor producing platelet degranulation such as an abnormal immunoglobulin. (
  • The first study selected, "The Use of Recombinant Factor VIIa in Children with Inherited Platelet Function Disorders" is considered a Level II study with regard to the amount of evidence provided by the controlled case study. (
  • The question examined in this paper is whether treatment with recombinant human factor VIIa helps to control bleeding in children with Glanzmann's Thrombasthenia. (
  • 4 5 Although thrombopoietin (TPO) plays a major role in regulating MK and platelet production, 6-8 many studies point to additional contributions from stem cell factor (SCF), interleukin-3 (IL-3), interleukin-6 (IL-6), interleukin-11 (IL-11), granulocyte-macrophage colony-stimulating factor (GM-CSF), and basic fibroblast growth factor (bFGF). (
  • Vitreous platelet and endothelial microparticles levels were increased in diabetic patients and decreased following panretinal laser photocoagulation or intravitreal antivascular endothelial growth factor injection in proliferative diabetic retinopathy (PDR). (
  • The signs and symptoms of platelet disorders are different from those of coagulation factor deficiencies (disorders of secondary hemostasis). (
  • Having cell lines will permit testing of future candidate risk factor genes. (
  • K562 Cells Produce an Anti-Inflammatory Factor That Inhibits Neutrophil Functions In Vivo," Blood 80:1546-1552 (1992). (
  • Clements et al, "Secretion of human epidermal growth factor from Saccharomyces cerevisia using synthetic leader sequences," Gene 106:267-272 (1991). (
  • The aim of this study is to investigate the effect of the chimeric intron in different directions on the expression of the nerve growth factor (NGF) in recombinant Chinese hamster ovary (CHO) cells. (
  • The platelet fibrinogen receptor: an immunogold-surface replica study of agonist-induced ligand binding and receptor clustering. (
  • 2C9.G3 has also been reported in blocking of ligand binding and some adhesive processes. (
  • ITGAV:ITGB3 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1 (PubMed:18635536, PubMed:25398877). (
  • Some of these mechanisms involve initial formation of receptor-ligand complexes, followed by transport of the ligand across the cell membrane. (
  • Platelet activation causes conformational changes of integrin GPIIb/IIIa (α IIb β 3 ), resulting in the exposure of its ligand-binding pocket. (
  • The currently used strategy of ligand-mimetic, conformation-unspecific GPIIb/IIIa blockade is discussed as a potential reason for those unexpected limitations and failures. (
  • The binding of ligand-mimetic blockers to GPIIb/IIIa causes a conformational change from a low- to a high-affinity GPIIb/IIIa receptor. (
  • Cells expressing wild-type or mutant α M β 2 and Fg or its derivatives have been used to dissect the molecular requirements for this receptor-ligand pair to mediate cell migration. (
  • Critical to the ligand-binding functions of the α M I domain is the metal ion-dependent adhesion site (MIDAS). (
  • Because the mutation that causes this disorder affects only one copy of the ITGA2B gene, some normal integrin is formed and normal platelets produced, which accounts for the mild signs and symptoms in affected individuals. (
  • Recent biochemical and cellular studies on shedding pathways 7-10 and surface expression 11-13 of GPVI illustrate some of the key mechanisms underlying platelet receptor proteolysis, and recent preclinical studies 14 show how significant these findings may be in the context of thrombotic risk. (
  • Generally speaking, acute inflammation is mediated by granulocytes, while chronic inflammation is mediated by mononuclear cells such as monocytes and lymphocytes. (
  • HLA typing revealed that the patient's T cells were of donor origin, while the B cells and monocytes were of host origin. (
  • Unlike H 2 DCFDA, Fc OxyBURST Green assay reagent does not require intracellular esterases for activation, making this reagent particularly suitable for detecting the oxidative burst in cells with low esterase activity such as monocytes. (
  • This progenitor gives rise to monocytes, macrophages, granulocytes (neutrophils, basophils, and eosinophils), and some tissue dendritic cells through differentiation steps including GPs and cMOPs. (
  • A recent study suggests that GMPs are a heterogeneous population of cells comprised of unipotent clones with a nonoverlapping potential to give rise to monocytes, macrophages, and granulocytes (11). (
  • Clopidogrel also inhibits platelet aggregation induced by agonists other than ADP, by blocking the amplification of platelet activation due to the released ADP. (
  • Since clopidogrel is a prodrug, it must be metabolized by CYP450 enzymes to produce the active metabolite that inhibits platelet aggregation. (
  • The body's reaction to vessel wall injury is rapid adhesion of platelets to the subendothelium. (
  • The isolated presence of large platelets in peripheral blood, in the absence of any other signs of bone marrow dysfunctions, is suggestive of normal activity. (
  • Platelet membrane glycoproteins are surface glycoproteins found on platelets (thrombocytes) which play a key role in hemostasis. (
  • This negative surface provides binding sites for enzymes and cofactors of the coagulation system, resulting in the formation of a clot (secondary hemostasis). (
  • Platelets are the main cellular component in blood responsible for maintaining the integrity of the cardiovascular system via hemostasis. (
  • The studies provide a link between the well-studied paradigms of platelet hemostasis and tumorigenesis. (
  • Platelet disorders lead to defects in primary hemostasis. (
  • Although platelets (PLTs) play critical roles in hemostasis, 1 angiogenesis, 2 and innate immunity, 3 PLT production remains poorly understood. (
  • Fibrinogen, which had been released from the alpha-granules of these cells, bound to GPIIb-IIIa on the cell surface and was similarly clustered. (
  • Organelle zone - is rich in platelet granules. (
  • Platelets contain two unique types of granules: alpha granules and dense granules. (
  • Thus, abnormalities of platelet glycoproteins, platelet granules, and signal transduction and secretion can all result in hemorrhagic diatheses and prolonged bleeding times. (
  • Once platelets are activated, granules secrete clotting mediators, including both ADP and TXA2 . (
  • During platelet activation, the granules are released out of the platelets. (
  • Mucocutaneous bleeding manifestations and platelet dysfunction consistent with GT were observed in three members of a Cypriot family: a 3-year-old proband, her father and her paternal uncle. (
  • In addition, platelet αIIbβ3 deficiency or dysfunction should always be confirmed. (
  • Nevertheless, the same patients have substantially increased risk of bleeding due to platelet dysfunction and intake of certain medications (antiaggregants, heparin and low‐molecular weight heparins, and anemia). (
  • Conclusions This novel autosomal dominant macrothrombocytopenia associated with platelet dysfunction raises interesting questions about the role of integrin β 3 , and its βTD domain, in platelet formation and function. (
  • PfEMP1 presentation, platelet activation and astrocyte dysfunction were identified as the key events influencing the disease. (
  • and mechanisms underlying the killing of malignant cells by some drugs used in chemotherapy are not confined to this chapter but presented in the relevant chapters dealing with pharmacologically different groups of drugs. (
  • Once activated, platelets have two major mechanisms to recruit additional platelets to the growing hemostatic plug. (
  • Platelet-surface sheddases, particularly of the metalloproteinase-disintegrin (ADAM) family, can be regulated by many of the same mechanisms that control receptor function, such as calmodulin association or activation of signaling pathways. (
  • This suggests there may be common mechanisms for switching on both extracellular and intracellular proteolytic pathways, to regulate adhesion and signaling in platelets or other cells. (
  • Therefore, it is very important to understand the mechanisms employed by S. aureus to colonize and proliferate in these cells. (
  • This review discusses our current understanding of the regulatory mechanisms of platelet- neutrophil interactions in thromboinflammatory disease. (
  • Watkins LC, DeGrado WF, Voth GA. Influenza A M2 Inhibitor Binding Understood through Mechanisms of Excess Proton Stabilization and Channel Dynamics. (
  • Development of atherosclerotic plaques also includes the continuous crosstalk between EC, smooth muscle cells (SMCs), inflammatory cells, and inflammatory mediators ( 1 ) acting through mechanisms that have not yet been completely revealed. (
  • This complex interacts with fibrinogen and thus plays an important role in platelet aggregation and adhesion to endothelial surfaces. (
  • Fg also has been shown to bridge α M β 2 -bearing leukocytes to intercellular adhesion molecule (ICAM)-1 on endothelial cells ( 17 )( 18 ). (
  • Patients with GT are classified as having type 1, type 2, or variant type based on the degree of GP IIb-IIIa deficiency, fibrinogen binding, and clot retraction. (
  • Additionally, they have absent fibrinogen binding and clot retraction. (
  • however, fibrinogen binding and clot retraction widely vary. (
  • Glanzmann thrombasthenia (GT) is an autosomal recessive bleeding disorder characterized by lack of platelet aggregation induced by most agonists. (
  • Background Defects of integrin α IIb β 3 are typical of Glanzmann's thrombasthenia, an inherited autosomal recessive bleeding disorder characterized by the failure of platelets to aggregate in response to all physiological agonists, but with no abnormalities in the number or size of platelets. (
  • Individuals with type 2 have 10-20% of GP IIb-IIIa, can bind fibrinogen, and have normal-to-moderately deficient clot retraction capability. (
  • In type I, platelets show absence of the glycoprotein IIb/beta-3 complexes at their surface and lack fibrinogen and clot retraction capability. (
  • In type II, the platelets express the glycoprotein IIb/beta-3 complex at reduced levels (5-20% controls), have detectable amounts of fibrinogen, and have low or moderate clot retraction capability. (
  • Platelets , also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors ) is to react to bleeding from blood vessel injury by clumping, thereby initiating a blood clot . (
  • The hemostatic system consists of platelets, coagulation factors, and the endothelial cells lining the blood vessels. (
  • The design of the vasculature, or blood vessels, is such that the walls of the vessels are chemically inert to both coagulation factors and platelets under normal conditions. (
  • Clopidogrel, an inhibitor of platelet aggregation, selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet receptor and the subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation. (
  • The drug is an irreversible inhibitor of the P2Y12 adenosine diphosphate receptor found on the membranes of platelet cells. (
  • The active metabolite of clopidogrel prevents binding of adenosine diphosphate (ADP) to its platelet receptor, impairing the ADP-mediated activation of the glycoprotein GPIIb/IIIa complex. (
  • Receptor binding may also result in signal transduction ( Probes for Signal Transduction-Chapter 17 ), Ca 2+ mobilization ( Indicators for Ca2+, Mg2+, Zn2+ and Other Metal Ions-Chapter 19 ), intracellular pH changes ( pH Indicators-Chapter 20 ) and formation of reactive oxygen species (ROS, Probes for Reactive Oxygen Species, Including Nitric Oxide-Chapter 18 ). (
  • In medicine , glycoprotein IIb/IIIa ( GPIIb/IIIa , also known as integrin α IIb β 3 ) is an integrin complex found on platelets . (
  • GP9 encodes a small membrane glycoprotein found on the surface of human platelets. (
  • By blocking the amplification of platelet activation by released ADP, platelet aggregation induced by agonists other than ADP is also inhibited by the active metabolite of clopidogrel. (
  • The platelet aggregation was completely restored when higher concentration of agonists were used. (
  • Laboratory tests in severe GT show no platelet aggregation in response to all physiologic agonists and show reduced or absent clot reaction [ 5 ]. (
  • The platelet GP IIb/IIIa complex mediates platelet-to-platelet interactions (platelet aggregation). (
  • A disorder of platelet function is a thrombocytopathy . (
  • CD31/ PECAM-1 is a member of the immunoglobulin gene superfamily found on platelets, most leukocytes, and endothelial cells. (