Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, we described a platelet antibody against a putative collagen receptor (P62), which was found in a patient with idiopathic thrombocytopenic purpura (ITP) (Blood 69:1712). We now report a deficiency of the P62 receptor in a young man whose platelets showed defective collagen-induced platelet aggregation. He had a mild bleeding tendency and slight thrombocytopenia. The results of coagulation and fibrinolysis studies were normal. The patient's platelets were partially unresponsive to collagen, although aggregation in response to ADP, thrombin, ristocetin, and calcium ionophore (A23187) was almost normal. Adhesion of his platelets to bovine collagen was markedly reduced. Addition of collagen caused no synthesis of thromboxane (TX)B2 in platelet rich plasma (PRP) from this patient. Furthermore, collagen produced no rise of cytosolic free calcium ([Ca2+]i) in fura2-loaded platelets. In contrast, thrombin caused TXB2 formation and an increase of [Ca2+]i in his platelets. These results suggest defective interaction between the platelets and collagen. The IgG from the ITP-patient induced irreversible aggregation in normal PRP, but caused no aggregation of the young man's platelets. Immunoblot studies showed that normal platelets had antigens with a molecular weight of 62 KDa under reducing conditions and of 57 KDa under nonreducing conditions. In contrast, the young man's platelets had no P62 band, although GPIa/IIa and thrombospondin were normally present. These results indicate that impaired collagen-induced aggregation in the patient's platelets was due to a deficiency of P62 and confirm that P62 may play a crucial role as a collagen receptor in platelet activation.
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PMID:Deficiency of P62, a putative collagen receptor, in platelets from a patient with defective collagen-induced platelet aggregation. 131 Nov 44

Adhesion molecules play a crucial part in cell-matrix and in cell-cell interactions. These interactions, which are essential to the body's defense processes, involve adhesion molecules belonging to different families: integrins, immunoglobulins and selectins. Integrins are expressed by a large number of tissues, whereas other adhesion molecule families are restricted to a small number of cell types. A recent symposium dealt with the recruitment of circulating platelets at specific sites, their adhesion to extracellular matrix components and their activation by agonists leading to aggregation or attachment to other cells. These events, supporting hemostasis and thrombosis, involve integrins, selectins and other adhesion molecules. This report focuses on newly reported integrins (GPIa, GPIc, GPIIa), selectins (GMP-140) and GPIIIb, previously known as 'minor' surface oriented platelet glycoproteins. Major membrane glycoproteins such as GPIIb-IIIa (an integrin) and GPIb, which also play a vital role in platelet functions, have been extensively reviewed elsewhere.
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PMID:New families of adhesion molecules play a vital role in platelet functions. 220 5

Adhesion of platelets to the subendothelium is an essential step in hemostasis and thrombosis. Several receptors for adhesive macromolecules have been identified on platelets and are included in the integrin family. To clarify the role of platelet membrane glycoproteins in the interaction of platelets with the subendothelium, 51Cr-labeled platelet adhesion assay and antibody-blocking experiments were performed by using in vitro cultured subendothelium under the static condition. The platelet adhesion in this assay was inhibited by anti-GPIa (VLA-2), GPIc (VLA-5) and -GPIc'-(VLA-6) antibodies, while anti-GPIb and -GPIIb/IIIa antibodies had no effect. Platelets from the patients with Glanzmann's thrombasthenia could also attach to the subendothelium, whereas those from a patient whose platelets lacked GPIa failed to attach to the extracellular matrix (ECM). The monoclonal antibodies against fibronectin and laminin which recognized the cell binding domain of these molecules inhibited the platelet adhesion when they were pre-treated with ECM. Furthermore, antibody-blocking experiments revealed that the percent inhibition by the combination of anti-GPIa, -GPIc and -GPIc' antibodies used herein was approximately 75%. They did not completely inhibit the attachment. These results suggest that the interactions of collagen, fibronectin and laminin with their receptors on platelets are involved in the mechanism of platelet adhesion to subendothelium.
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PMID:Role of membrane glycoproteins in the interaction of blood platelets with the vessel wall--the study on platelet adhesion to in vitro cultured subendothelial matrix. 262 57

Platelet glycoprotein VI (GPVI), a 62kD membrane protein, has been identified as one of the platelet receptors for collagen, since GPVI-deficient platelets exhibit abnormal responses to collagen and an abnormal bleeding tendency. We report a female patient with a mild bleeding history whose platelets expressed 10% GPVI of normal platelets. Shape change, aggregation and ATP release of the patient's platelets were completely absent in response to 1-5 micrograms/ml collagen but present normally in response to ADP and Ca2+ ionophore A23187. Adhesion of the patient's platelets to coated collagen was mildly affected (40-60% of normal platelets) in spite of only 10% expression of GPVI. Flow cytometrical studies revealed that the patient's platelets expressed normal amounts of the GPIa/IIa complex. These results suggest that platelet GPVI is less involved in adhesion to collagen than shape change and aggregation induced by collagen.
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PMID:Platelets with 10% of the normal amount of glycoprotein VI have an impaired response to collagen that results in a mild bleeding tendency. 753 Apr 76

Adhesion of platelets to the damaged subendothelium is a prerequisite reaction for the initiation of hemostasis in vivo. Platelet membranes contain high concentrations of integrins and other glycoproteins (GPs) that are involved in the platelet adhesion to the extracellular matrix. In the present review, we focus on two platelet integrins, integrin alphaIIb beta3 (GPIIb/IIIa) and integrin alpha2 beta1 (GPIa/IIa) because these integrins are major components of the platelet membrane proteins and are known to contribute to platelet adhesion to fibrin(ogen) and collagen surfaces, respectively. These integrins bind soluble ligands (fibrinogen or collagen) after platelets are activated but only have low affinity towards these ligands when platelets are in the resting state. We describe the binding properties of these integrins and discuss the mechanism for the activation of these integrins. Platelets can adhere to fibrin(ogen) or collagen immobilized on a surface. When platelets adhere to a collagen- or fibrin-coated surface, they become activated and form aggregates; this is especially prominent under flow conditions. We discuss the contribution of these integrins and non-integrin proteins, GPIb and GPVI, to the platelet adhesion on to the collagen surface, especially under flow conditions, a system that most closely approximates platelet adhesion in vivo.
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PMID:Integrin-mediated platelet adhesion. 966 95

Liposomes carrying both recombinant platelet membrane glycoproteins GPIa/IIa (rGPIa/IIa) and GPIb alpha (rGPIb alpha) (rGPIa/IIa-Ib alpha-liposomes), or fibrinogen (Fbg-liposomes) were prepared. Their interactions with platelets on a collagen surface under flow conditions were evaluated using a recirculating flow chamber, mounted on an epifluorescence microscope, which allows for real-time visualization of fluorescence-labeled liposomes or platelets interacting with the surface. Adhesion of platelets to the collagen surface increased with increasing the shear rate from 600 to 2400 s(-1). Also, the percentages of surface coverage of rGPIa/IIa-Ib alpha-liposomes or Fbg-liposomes increased with increasing platelet adhesion. These phenomena were attenuated by a peptide containing arginine-glycine-aspartic acid (RGD-peptide), or prostaglandin E1 (PGE), but not by a peptide containing arginine-glycine-glutamic acid (RGE-peptide). In a homogeneous solution, rGPIa/IIa-Ib alpha-liposomes and Fbg-liposomes enhanced platelet aggregation in a dose-dependent manner, as evaluated using an aggregometer. These findings suggest that rGPIa/IIa-Ib alpha-liposomes and Fbg-liposomes form aggregates at the site of injury in blood vessels, resulting in stationary adhesion together with activated platelets.
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PMID:Platelet interactions with liposomes carrying recombinant platelet membrane glycoproteins or fibrinogen: approach to platelet substitutes. 1179 31

Decreased platelet aggregation to collagen is a cause for bleeding diathesis of Chediak-Higashi syndrome (CHS). We investigated whether the collagen receptor-Ca2+ signaling system was impaired in platelets from cattle affected with CHS. A collagen-induced increase in cytosolic Ca2+ ([Ca2+]i) was depressed in CHS platelets, which was accompanied by a decrease in the production of inositol 1,4,5-trisphosphate. When the influences of endogenous arachidonic acid metabolites and ADP were excluded, convulxin or collagen-related peptide, which are specific agonists for the collagen receptor GPVI, increased [Ca2+]i in both normal and CHS platelets. In contrast, rhodocytin, which was thought to activate another collagen receptor GPIa/IIa, increased [Ca2+]i in CHS platelets to a lesser extent than in normal ones. Cytochalasin D, an actin polymerization inhibitor, depressed the response to collagen or rhodocytin but not the response to convulxin. Adhesion of CHS platelets to acid soluble type I collagen, which was mediated by GPIa/IIa, was similar to that of normal platelets. These results suggest that a defect in the rhodocytin-sensitive pathway is responsible for decreasing the response to collagen in CHS platelets. It remains to be determined which receptor is associated with the mechanism.
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PMID:A defect in collagen receptor-Ca2+ signaling system in platelets from cattle with Chediak-Higashi syndrome. 1185 96

Acute thrombotic arterial occlusion is the leading cause of morbidity and mortality in the Western world. Von Willebrand factor is thought to be the only indispensable adhesive substrate to promote thrombus formation in high shear environments. We found that thrombospondin-1, a glycoprotein enriched in arteriosclerotic plaques, might function as an alternative substrate for thrombus formation. Platelets adhered to thrombospondin-1 in a shear dependent manner with an optimum shear as found in stenosed arteries. Adhesion is extremely firm, with no detachment of platelets up to a shear rate of 4000 s(-1). Experiments using platelets from a patient completely lacking von Willebrand factor showed that von Willebrand factor is not involved in platelet binding to thrombospondin-1. Platelet adhesion to thrombospondin-1 is not mediated via beta3-integrins or GPIa. CD36 partially mediates the adhesion of pre-activated platelets. We identified GPIb as high shear adhesion-receptor for thrombospondin-1. Soluble GPIb, as well as antibodies against the GPIb, blocked platelet adhesion almost completely. The new discovered thrombospondin-1-GPIb adhesion axis under arterial shear conditions might be important, not only during thrombus formation but also for pathological processes where other cells bind to the endothelium or subendothelium, including arteriosclerosis, inflammation and tumor metastasis, and a promising therapeutic target.
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PMID:Thrombospondin-1 mediates platelet adhesion at high shear via glycoprotein Ib (GPIb): an alternative/backup mechanism to von Willebrand factor. 1282 98

The 807 C/T dimorphism in the GPIa gene has been shown to affect GPIaIIa receptor density, which can affect platelet adhesiveness to collagens. In this work, we studied platelet function mediated by GPIaIIa. The 807 T/T genotype was associated with increased platelet adhesion to monomeric collagen after activation with ADP, but not following activation with thrombin and U46619. Adhesion to fibrillar collagen and PFA-100 closure time were not different between carriers of the C/C and T/T genotypes. Also, to monitor the role of the 807 C/T polymorphism in the sensitivity to platelet antagonists, anti-GPIaIIa monoclonal antibodies (Gi9) were used. Irrespective of the 807 C/T genotype, Gi9 inhibited the ADP-induced platelet adhesion to the monomeric collagen-coated surface stronger than adhesion evoked by thrombin. Moreover, Gi9 significantly inhibited platelet adhesion to both monomeric and fibrillar collagen in 807 T/T carriers, whereas in 807 C/C subjects, Gi9 blocked only adhesion to monomeric collagen. Our results indicate that the 807 T/T genotype is related to increased platelet activation induced by ADP and higher platelet sensitivity to GPIaIIa antagonists.
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PMID:Effect of the 807 c/t polymorphism in glycoprotein ia on blood platelet reactivity. 1463 Nov 12

Collagen, one of the major proteins of sub-endothelial vasculature get exposed following endothelium denudement, is a potent stimulator of platelet adhesion and aggregation. Adhesion of platelets following endothelial injury is the primary event usually associated with uncontrolled platelet activation culminating into intravascular thrombosis, thus needs to be intervened to prevent the pathology related to various peripheral, myocardial and cerebral ischemic episodes. Recent advances in the understanding of collagen mediated platelet adhesion and aggregation have led to the identification of two prominent receptors, glycoprotein Ia/IIa (GPIa/IIa or integrin alpha(2)beta(1)) and glycoprotein VI (GPVI) and associated intracellular signaling, which are undoubtedly the new emerging targets for the development of more effective antithrombotic drugs. The optimism for collagen antagonism is based on results obtained so far by the use of monoclonal and polyclonal antibodies, peptide inhibitors, knockouts models and collagen-mimetics in various in vitro test systems and animal models. These findings have revealed that collagen receptor inhibition is an attractive and secure strategy for the new drug development to prevent intravascular thrombosis.
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PMID:Platelet collagen receptors, signaling and antagonism: emerging approaches for the prevention of intravascular thrombosis. 1804 62


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