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)

Human Factor VIII associated von Willebrand factor (VIII:vWF) binds to human platelets in vitro only in the presence of a mediator such as ristocetin, thrombin or ADP. Studies reported here were designed to determine if human platelets will adhere to solid-phase VIII:vWF. Human VIII:vWF was purified from a phosphate precipitate of A1(OH)3 absorbed plasma using 4% agarose and DEAE cellulose. Purified VIII:vWF (90 units of VIII:vWF activity/mg) was coated on dialysis membranes using ultrafiltration (final concentration of 0.4 units/cm2). Membranes (0.5 cm2) were held stationary in human citrated PRP suspension or washed platelet suspensions and stirred continuously for 5 minutes at 37 degrees C. The membranes were then rinsed in phosphate buffered saline, fixed, stained, and examined by light and scanning electron microscopy. Abundant normal platelets adhered to VIII:vWF-coated membranes, while minimal adhesion was seen on uncoated membranes and membranes coated with albumin. Adhesion occurred without ristocetin, thrombin, ADP or other agonist and in the presence of Ca+2/Mg+2 ions. Preincubation of the VIII:vWF coated membranes with monospecific rabbit anti-VIII:vWF inhibited the adhesion reaction. However, preincubation of VIII:vWF coated membranes with naturally occurring human anti-FVIIIc antibodies failed to interfere with platelet adhesion. Platelets from a patient with Bernard-Soulier Syndrome (BSS) which did not bind human VIII:vWF in the presence of ristocetin or aggregate with bovine cryoprecipitate also did not adhere to VIII:vWF-coated membranes.
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PMID:Adhesion of human platelets to purified solid-phase von Willebrand factor: studies of normal and Bernard-Soulier platelets. 641 73

Heparin inhibited monolayer adhesion of washed human and rabbit platelets to collagen-coated glass at 2.5 and 20 units/ml concentration, in the absence of red cells. Adhesion of rabbit platelets to de-endothelialized rabbit aorta, under similar conditions, was less strongly inhibited but no inhibition was seen at 40% haematocrit. Addition of plasma reduced, rather than enhanced heparin activity and hirudin 0.5 units/ml had no significant effect. Heparin also inhibited platelet aggregation, release of (14C) 5-HT and production of malondialdehyde in response to collagen and thrombin. Inhibition of thrombin-induced activity was greater in the presence of plasma. However, heparin enhanced aggregation and release evoked by ADP and did not consistently inhibit MDA synthesis produced by arachidonate. The results indicate that in addition to the effects of heparin on platelet function mediated by anti-thrombin activity and the previously described augmentation of responses to ADP, heparin has weak inhibitory activity against platelet-collagen interactions. Binding of heparin to the platelet membrane (and to surfaces to which platelets adhere) could account for these findings by causing non-specific interference with agonist-receptor interactions.
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PMID:Effect of heparin on platelet monolayer adhesion, aggregation and production of malondialdehyde. 710 Dec 45

Adhesion of human platelets to type I collagen under arterial flow conditions is extremely fast, being mediated primarily by the alpha 2 beta 1 integrin (glycoprotein Ia/IIa). We have investigated the involvement of cyclic nucleotides in platelet adhesion to soluble native collagen immobilized on Sepharose beads using a new microadhesion assay under arterial flow conditions. To prevent platelet stimulation by thromboxanes and adenosine diphosphate (ADP), experiments were performed with aspirin-treated platelets in the presence of ADP-removing enzyme systems such as creatine phosphate/creatine phosphokinase or apyrase. Rapid reciprocal changes in platelet adenosine 3'5'-cyclic monophosphate (cAMP) and guanosine 3'5'-cyclic monophosphate (cGMP) occurred during adhesion. cAMP levels in adherent platelets were 2.4-fold lower than in effluent platelets or in static controls, whereas cGMP levels were increased 2.4-fold. These results suggest that contact between platelets and collagen stimulates guanylate cyclase and inhibits adenylate cyclase. This occurs in the absence of the platelet release reaction. We also studied short-term effects of agents that regulate cyclic nucleotide synthesis, prostaglandin E1 (PGE1) and sodium nitroprusside (SNP). After only 3.8 seconds at 10 to 30 dyne/cm2, PGE1 (10 mumol/L) increased cAMP 16.4-fold, whereas SNP (50 mumol/L) increased cGMP ninefold and caused a 3.2-fold increase in cAMP. Both PGE1 and SNP rapidly (< 5 seconds) inhibited platelet adhesion in a dose-dependent manner that was correlated with the increase in cyclic nucleotides. Our data suggest that cAMP and cGMP play a regulatory role in the initial phases of platelet adhesion to collagen mediated by the alpha 2 beta 1 integrin receptor.
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PMID:Role of cyclic nucleotides in rapid platelet adhesion to collagen. 751 2

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

Four disintegrins, eristostatin, albolabrin, barbourin and echistatin, injected IV into C57BL/6 mice in combination with B16F10 murine melanoma cells, inhibited formation of experimental lung metastases with ID50s of 0.05, 1.0, 0.9, and 3.7 mumoles per mouse, respectively. When injected 1 h after tumor cells, albolabrin, echistatin and barbourin had the same antimetastatic activity, while eristostatin was not active. Eristostatin (IC50 7-8 nM) was more potent than echistatin (IC50 74-75 nM), barbourin (IC50 46-60 nM), and albolabrin (IC50 130-165 nM) as an inhibitor of murine platelet aggregation induced by ADP or tumor cells. Fibronectin was the best substrate for melanoma cell adhesion (95%), followed by laminin (47%) and vitronectin (24%). Albolabrin was the strongest and eristostatin the weakest inhibitor of cell adhesion to all substrata. Adhesion of melanoma cells to albolabrin, echistatin, and barbourin was partially inhibited by monoclonal antibody against mouse alpha v subunit. This antibody bound to B16F10 melanoma cells in suspension and inhibited binding of fluorescein isothiocyanate (FITC)-labeled disintegrins to these cells, being the most effective with FITC-labeled albolabrin. Our study suggests that a major contribution of eristostatin to inhibition of lung colonization is via preferential binding to platelet alpha IIb beta 3 integrin and blocking tumor cells interaction with platelets. A major contribution of albolabrin, barbourin and echistatin appears to be by interference with other integrin receptors on the tumor cell surface. Albolabrin appeared to inhibit RGD-dependent integrins containing alpha v subunit, such as alpha v beta 3 and alpha v beta 1.
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PMID:Effect of four disintegrins on the adhesive and metastatic properties of B16F10 melanoma cells in a murine model. 754 46

Magnesium deficiency and its association with platelet hyperreactivity has been well recognised in a variety of diseases including myocardial infarction, preeclampsia, and diabetes. In order to investigate potential effects of intravenous Mg2+ supplementation, platelet function was studied by measurements of in vitro bleeding time (BT) and of fibrinogen (Fg)-mediated aggregation of washed platelets. In addition, the effect of Mg2+ on platelet adhesion onto immobilised Fg, on Fg binding to activated platelets, and on surface expression of GMP-140 or GP53 was evaluated. Mg2+ (4 mM) prolonged in vitro BT by 30% and inhibited Fg-mediated aggregation significantly, independent of the agonist used to initiate platelet aggregation (ADP, collagen, epinephrine, thrombin, phorbol ester). Adhesion of resting platelets to immobilised Fg was reduced by 50% in the presence of 2 mM Mg2+. Moreover, Mg2+ reduced Fg binding to ADP- or collagen-stimulated platelets as well as surface expression of GMP-140 with an IC50 of approximately 3 mM. Intravenous administration of Mg2+ to healthy volunteers inhibited both ADP-induced platelet aggregation (p < 0.05) by 40% and binding of Fg or surface expression of GMP-140 by 30% (p < 0.05). Thus, pharmacological concentrations of Mg2+ effectively inhibit platelet function in vitro and ex vivo.
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PMID:Effects of magnesium on platelet aggregation and adhesion. Magnesium modulates surface expression of glycoproteins on platelets in vitro and ex vivo. 774 Apr 63

The effect of doxazosin, a selective alpha-1 adrenergic inhibitor, on hemostasis was investigated in 9 cynomolgus monkeys. During 12 weeks of doxazosin treatment (1 mg/kg per day), serum lipids, lipoprotein cholesterols, blood coagulation, platelet aggregation and template bleeding times were measured and compared with predrug values. In addition, platelet adhesion to cultured human umbilical vein endothelial cells (HUVEC) in the presence or absence of doxazosin was evaluated. Platelet aggregation was also determined in monkeys following chronic oral exposure to aspirin (162 mg/day). Doxazosin administration was associated with significant reductions in serum total cholesterol (TC) (-16%) and low density lipoprotein cholesterol (LDL-C) (-23%), while high density lipoprotein cholesterol (HDL-C) levels increased 66%. Doxazosin did not alter any parameters of blood coagulation measured; however, bleeding times were increased significantly (33%) in doxazosin-treated animals. Although collagen-stimulated platelet aggregation was not influenced by either chronic doxazosin or aspirin treatment, the maximal extent of ADP-stimulated platelet aggregation was significantly reduced (-26% and -18%, respectively) compared with the control monkeys. Platelets from untreated control animals displayed reductions in the extent of ADP-stimulated aggregation of 13% and 23%, respectively, when incubated in vitro with 200 and 300 micrograms/ml of doxazosin. Additionally, the decrease in aggregation response of platelets obtained from doxazosin-treated monkeys was accompanied by a rapid reversal of platelet aggregation. Adhesion to HUVEC by platelets isolated from doxazosin-treated animals was significantly decreased; however, adhesion was not altered when platelets from untreated control animals were incubated with HUVEC in the presence of doxazosin. Thus, the ex vivo and in vitro studies reported in this communication suggest that doxazosin administration to nonhuman primates is associated with beneficial alterations in plasma lipids, platelet aggregation, bleeding times and platelet adhesion to endothelial cells, parameters which are thought to influence risk of cardiovascular disease in both animals and humans.
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PMID:The effects of doxazosin on platelet aggregation, platelet adhesion and blood coagulation in cynomolgus monkeys. 794 57

Platelet membrane glycoproteins Ib (GPIb) and IIb/IIIa (GPIIb/IIIa) bind soluble von Willebrand factor (vWf) after stimulation with ristocetin (GPIb) or with thrombin or ADP (GPIIb/IIIa). In fluid-phase, vWf does not bind to these platelet receptors without stimulation. In contrast, platelets adhere to solid-phase vWf without stimulation by ristocetin, adenosine diphosphate (ADP), or thrombin, and adhesion increases after stimulation by these agonists. The effect of monoclonal antibodies specific for GPIb (6D1) and GPIIb/IIIa (10E5 and HP1-1D) on platelet adhesion to solid-phase vWF was studied. Adhesion of radiolabeled, washed platelets (with washed red blood cells) aspirated at a constant wall shear rate of 1000 sec-1 through glass capillary tubes coated with purified human vWf was quantified. Unstimulated platelet adhesion was decreased 80% to 90% by blocking either the GPIb site or the GPIIb/IIIa site with 6D1 or 10E5, respectively, or with 6D1 and 10E5 together. Adhesion was not reduced significantly by HP1-1D (anti-GPIIb/IIIa). After stimulation with ADP or thrombin, the platelet adhesion was reduced by prior incubation with saturating concentrations of either 6D1 (61% reduction) or 10E5 (80% reduction), as well as with both 6D1 and 10E5 (80% reduction). After stimulation with ristocetin, the adhesion was reduced with either 6D1 (90% reduction) or 10E5 (90% reduction) or both 6D1 and 10E5 (90% reduction). Prior incubation with HP1-1D had minimal effect on platelet adhesion to vWF after stimulation with thrombin, ADP, or ristocetin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Monoclonal antibodies to platelet glycoproteins Ib and IIb/IIIa inhibit adhesion of platelets to purified solid-phase von Willebrand factor. 805 92

We investigated the molecular mechanism(s) by which platelets adhere to an artificial surface exposed to plasma, using polystyrene microtiter plates pretreated with plasma. Washed platelets labelled with 51Cr were incubated with the plates under static conditions. Prostaglandin E1(PGE1) was added to the platelets to prevent platelet-platelet interactions. Adhesion required the presence of a divalent cation such as Mg++ or Ca++. Polyclonal anti-fibrinogen antibody inhibited adhesion by 70%. Polyclonal antibodies against fibronectin, vitronectin, von Willebrand's Factor, and the Fc portion of human IgG, had no effect on adhesion. Platelets adhered normally to a surface pretreated with plasma from a patient with severe von Willebrand's disease. No platelet adhesion occurred when the surface was pretreated with an afibrinogenemic plasma. Monoclonal antibodies against platelet membrane GPIIb-IIIa, potent inhibitors of ADP-induced fibrinogen binding to platelets, completely inhibited adhesion. Monoclonal antibodies against the GPIb alpha subunit and GPIc(VLA alpha 5) showed no inhibitory effects on adhesion. Platelets from a patient with Glanzmann's thrombasthenia (type I) did not adhere to the surface pretreated with normal plasma. These results suggest that plasma fibrinogen adsorbed onto the surface and that platelet membrane glycoprotein(GP)IIb-IIIa were responsible for adhesion in an activation-independent manner.
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PMID:Evidence that plasma fibrinogen and platelet membrane GPIIb-IIIa are involved in the adhesion of platelets to an artificial surface exposed to plasma. 813 6

Adhesion of resting and stimulated platelets to immobilized fibrinogen (Fg) was characterized using various forms of Fg, receptor peptide mimics, and antibodies to glycoprotein (GP) IIb/IIIa and Fg. Resting platelets adhered to Fg, but to less than half the extent of the same platelets stimulated with epinephrine/ADP. The adhesion of resting and stimulated platelets to Fg was inhibited by a receptor peptide mimic (G13, a peptide corresponding to residues 300-312 of GPIIb), anti-GPIIb/IIIa antibodies, and a monoclonal antibody (4A5) against the carboxyl terminus of the gamma chain of Fg. The results presented here demonstrate that the alpha chain RGD platelet recognition sites are not required to mediate the adhesion of either stimulated or resting platelets to immobilized Fg. Although stimulated platelets can adhere extensively to monomeric Fg containing one functional gamma chain, resting platelets require bivalent Fg containing two functional gamma chains to mediate irreversible adhesion to Fg.
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PMID:Characterization of adhesion of "resting" and stimulated platelets to fibrinogen and its fragments. 836 34


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