Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Platelets”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 613 records · Page 34Linked to original sources
PubMed1989

Effects of 3-azidothymidine on platelet counts, indium-111-labelled platelet kinetics, and antiplatelet antibodies.

Treatment of the acquired immunodeficiency syndrome with 3-azidothymidine (zidovudine; AZT) can induce severe neutropenia and anemia, while platelet counts increase. In order to understand the mechanism by which this favorable effect on platelets is induced, we prospectively studied platelet kinetics and platelet serology in 8 hemophiliacs receiving the drug. All patients underwent a second investigation after 3 months of treatment. Four patients were thrombocytopenic before treatment. Platelet counts increased significantly already after 1 week of treatment (p = 0.03), when only 3 patients remained thrombocytopenic. In these latter patients a further increase of platelet counts was noticed during the following 3 months. Platelet life-span was shortened in all patients at the initial investigation and a significant prolongation was measurable at the second evaluation (p = 0.015). Platelet-associated immunoglobulin G was increased in 3 patients at the first investigation and in 4 patients at the follow-up. Platelet-associated complement (PAC3d) was elevated in all subjects at the first determination. It decreased in 6, but increased in 2 patients thereafter; thus these changes did not become significant (p = 0.078). Immunofluorescence studies revealed antiplatelet antibodies in 7 patients' sera before treatment, and in 5 sera during drug therapy. At both investigations, the antibodies bound to the platelet glycoprotein IIIa as was demonstrated by immunoprecipitation of radiolabeled platelet proteins. We conclude, that AZT treatment improves platelet counts in HIV-infected hemophiliacs primarily by a prolongation of platelet survival without having a significant influence on antiplatelet antibody binding.

Autoantibodies↗
PubMed1988

The effect of exercise on platelet beta-adrenoceptor function and platelet aggregation in healthy human volunteers.

UNLABELLED: Plasma levels of adrenaline and noradrenaline, platelet cyclic-AMP (cAMP) content, platelet aggregation, platelet release of beta-thromboglobulin, and platelet factor 4 and serum content of thromboxane B2(TXB2) and 6-keto-PGF1 alpha were measured in 12 healthy male volunteers (age 38-72, mean 54.2 years) who were tested at rest and immediately after five min light cycle exercise. The plasma levels of adrenaline and noradrenaline increased significantly after exercise (P less than 0.01). The platelet cAMP level was not changed by exercise. The functional capacity of platelet beta-adrenoceptors, determined as cAMP production after beta-adrenoceptor stimulation in vitro, decreased highly significantly after exercise in all 12 volunteers (P less than 0.01). No alteration was observed in platelet aggregation induced by adrenaline or in platelet release of beta-thromboglobulin or platelet factor 4. No change was observed in the serum levels of TXB2 and 6-keto-PGF1 alpha. IN CONCLUSION: light cycle exercise results in a decreased functional capacity of platelet beta-adrenoceptors, but has no effect on platelet aggregation or platelet release. This might indicate a concomitant and equal decreased functional capacity of platelet alpha-adrenoceptors.

Adult↗
PubMed1994

Bernard-Soulier syndrome: quantitative characterization of megakaryocytes and platelets by flow cytometric and platelet kinetic measurements.

Platelets and megakaryocytes have been characterized in a Bernard-Soulier syndrome (BSS) kindred with respect to glycoprotein (GP) membrane receptors and measurements of thrombocytopoiesis. The index patient exhibited lifelong bleeding tendency, moderate thrombocytopenia (35 x 10(9)/l), giant platelets (mean platelet volume 12.5 microns 3 compared to 7.5 +/- 1.5 microns 3 in normals), absent ristocetin-induced platelet agglutination and absent binding of von Willebrand factor (vWF). Flow-cytometric analysis revealed absent platelet binding (0-2%) of monoclonal antibodies (mAb, LJ-P3, LJ-Ib1 and LJ-Ib10) directed against distinct epitopes on membrane GPIb alpha of the GPIb-IX complex, and normal binding of LJ-P4 mAb directed against GPIIb/IIIa complex (relative to increased platelet surface area). Marrow megakaryocytes also failed to express GPIb-IX complex, but demonstrated normal expression of GPIIb/IIIa. Among 6 asymptomatic family members, the patient's mother and 2 of his 4 children exhibited approximately 50% binding of anti-GPIb alpha mAb to their platelets by both flow cytometry and direct binding studies using 125I-vWF, 125I-LJ-Ib1 and 125I-LJ-Ib10 mAb. Marrow megakaryocytes were increased in the average cell volume and cytoplasmic granularity with a corresponding increase in ploidy (46% > 16N compared to 22 +/- 5% in normal individuals), a pattern typical of megakaryocytes stimulated by thrombocytopenia. Autologous 111In-platelet life span was shortened to 4.1 days (compared with 9.5 +/- 0.5 days in normal subjects), and the turnover of platelet mass in the circulation was near normal. The data directly demonstrate that the platelet membrane GPIb-IX defect in BSS originates in megakaryocytes at all levels of cell maturation, and exclude the possibility that the receptor abnormality is acquired during cell maturation or after platelets are released into the circulation. Since marrow megakaryocytes exhibited cellular changes consistent with stimulated megakaryocytopoiesis, these results also suggest that thrombocytopenia in this kindred of BSS is a consequence of both decreased platelet survival and ineffective platelet production.

Adult↗
PubMed1981

Platelet-vessel-wall interactions: experiences with von Willebrand platelets.

Adhesion of platelets from 15 patients with von Willebrand's disease was tested in an ex vivo human umbilical vein model. Experiments employed umbilical veins still in their umbilical cords taken from patients undergoing cesarean section and platelets (fetal, adult and vW) either apyrase-washed or used as platelet-rich plasma or whole blood. F VIII R:Ag, F VIII:Rcof, and F VIII:C were measured in initial fresh plasma and in effluents from the umbilical vein segments. F VIII:Rcof increased in most perfusates. Binding of latex-linked specific antihuman F VIII R:Ag demonstrated that F VIII R:Ag existed on subendothelium and on injured endothelial cells. Scanning electron microscopy three-dimensionally displayed vW platelet--vessel-wall interactions. Although vW platelets adhered to injured vein, both qualitative and quantitative differences existed in comparison with adhesion of normal platelets. The differences correlated best with the plasma F VIII:Rcof level. The best adhesion shown by vW platelets was only 51 percent of the adhesion of control fetal or adult platelets. vW platelets had less surface activity, fewer pseudopods, and little ability to spread and pave the exposed subendothelium. Pretreatment of the vein with F VIII R:Ag antibody partly blocked adhesion. Coperfusion of cryoprecipitate with vW platelets improved their adhesivity, state of activation on subendothelium, and ability to form aggregates. ABO differences in blood cell types of fetal material and platelet donors seemed without effect, which further establishes this model's validity for studies of platelet dysfunction and platelet or endothelial reactive agents.

Animals↗
PubMed1972

The mechanism of adenosine diphosphate induced platelet aggregation: binding to platelet receptors and inhibition of binding and aggregation by prostaglandin E 1 .

1. Normal human blood platelets in stirred plasma were incubated with [(14)C]ADP for 10-360 sec and the aggregation responses were correlated with platelet bound radioactivity, the platelets being separated from the plasma within 25 sec of the end of the experiment.2. The platelet aggregation response, measured as a change in light transmittance through platelet-rich plasma, was related to the plasma [(14)C]ADP concentration and linearly related to the log platelet bound [(14)C]ADP 60-120 sec after addition of nucleotide to plasma.3. Thin layer chromatography of the platelet bound radioactivity showed that 78-90% was unmetabolized ADP, the remainder being AMP. Plasma radioactivity consisted of ADP, AMP and adenosine. There was no detectable radioactive cyclic AMP in either platelets or plasma.4. Further accumulation of radioactivity occurred after 180 sec but was not related to the aggregation response.5. Prostaglandin E(1) inhibited aggregation and platelet [(14)C]ADP accumulation when added to platelet-rich plasma 60 sec before [(14)C]ADP. There was a significant correlation between inhibition of aggregation and inhibition of [(14)C]ADP accumulation.6. Prostaglandin E(1) also reversed ADP aggregation when added to platelet-rich plasma after the nucleotide, with an accompanying decrease in platelet bound [(14)C]ADP.7. It is concluded that ADP induces platelet aggregation by binding to specific receptors probably located on the plasma membrane, and that prostaglandin E(1) inhibits this effect by interfering with the ADP binding.

Adenine Nucleotides↗
PubMed1992

Platelet cGMP, but not cAMP, inhibits thrombin-induced platelet adhesion to pulmonary vascular endothelium.

We have compared the effects of intracellular pathways initiated by nitric oxide and prostacyclin on thrombin-induced platelet adhesion to endothelial cells. Platelet aggregate adhesion was enhanced when endothelial monolayers were pretreated with NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide production. In addition, decreased platelet aggregate adhesion was seen when platelets were pretreated with 8-bromoadenosine 3',5'-cyclic monophosphate (8-bromo-cAMP) or 8-bromoguanosine 3',5'-cyclic monophosphate (8-bromo-cGMP). Single platelet adhesion in isolated perfused lungs under flow conditions in the presence of shear was also assessed. Pretreatment of platelets with either Iloprost, in a dose sufficient to decrease platelet aggregation, or 8-bromo-cAMP did not affect platelet adhesion. However, pretreatment of platelets with 8-bromo-cGMP significantly reduced single platelet adhesion to endothelium. These studies illustrate that nitric oxide inhibits platelet adhesion to endothelium in the presence of shear. They further indicate that prostacyclin is also a regulator of this response but has effects more specifically related to the inhibition of platelet aggregation than platelet-endothelium interactions.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1997

Diabetic human platelets release a substance that inhibits platelet-mediated vasodilation.

This study was performed to investigate the mechanism for impaired vasodilation in response to activated diabetic human platelets. As observed previously, diabetic platelets failed to cause vasorelaxation, whereas normal platelets produced normal vasodilation. However, when activated and perfused through quiescent, NG-nitro-L-arginine-pretreated arteries, diabetic and normal platelets caused similar degrees of vasoconstriction. Inhibition of serotonergic and thromboxane A2 receptors in preconstricted normal arteries also failed to improve vasodilatory responses to diabetic platelets. The amount of ADP released into the supernatant from activated diabetic and normal platelets was similar. Concomitant perfusion of activated diabetic platelets impaired vasodilation produced by abluminally applied acetylcholine but perfusion of normal platelets did not. Whereas activated diabetic platelets failed to produce vasodilation, supernatant from the same platelets caused normal vasorelaxation. Dimethylthiourea and Tiron, intracellular free radical scavengers, normalized the vasodilatory response to diabetic platelets, whereas superoxide dismutase, catalase, and mannitol did not. We conclude that the impaired vasorelaxation in response to activated diabetic platelets is caused by an unidentified, short-acting, platelet-derived substance(s) that interferes with the normal dilatory response.

Acetylcholine↗
PubMed2005

Neutrophil P-selectin-glycoprotein-ligand-1 binding to platelet P-selectin enhances metalloproteinase 2 secretion and platelet-neutrophil aggregation.

Platelets and neutrophils constitute a high source of metalloproteinases (MMPs), and their interactions via P-selectin and P-selectin-glycoprotein-ligand-1 (PSGL-1) are involved in thrombosis, vascular remodelling, and restenosis. We investigated the impact of these interactions on platelet MMP-2 secretion and function in platelet and neutrophil aggregation. The secretion of MMP-2 from human platelets was significantly increased three-fold after thrombin activation, and enhanced two-fold in the presence of neutrophils. Neutrophil supernatant had no effect on platelet MMP-2 secretion. While no MMP-2 was detected in the supernatant of neutrophils, a high amount of MMP-9 was released by neutrophils, and remained unchanged upon thrombin activation or in the presence of platelets. Platelet P-selectin, which increased significantly after activation, triggered platelet binding to neutrophils that was completely inhibited by P-selectin or PSGL-1 antagonists, and was reduced by 50% with a GPIIb/ IIIa antagonist. P-selectin or PSGL-1 antagonism abolished the enhanced secretion of platelet MMP-2 in the presence of neutrophils and reduced platelet-neutrophil aggregation. Platelet activation and binding to neutrophils enhance the secretion of platelet MMP-2 via an adhesive interaction between P-selectin and PSGL-1, which contribute to increase platelet-neutrophil aggregation.

Antibodies↗
PubMed1976

Leukocyte-platelet interaction. Release of hydrogen peroxide by granulocytes as a modulator of platelet reactions.

Because of the many potent biological capabilities of the blood granulocytes, and their contact with platelets in various physiologic and pathologic states, a possible interaction between granulocytes and platelets was investigated. Platelets were purified by gel filtration and via a dialysis membrane were separated from suspensions of autologous granulocytes prepared by dextran sedimentation and resuspended in modified Tyrode's buffer. After 20 min at 37 degrees C platelet aggregation was shown to be diminished by such exposure, as compared to the aggregation of platelets incubated with dialysates of buffer only. When granulocytes were stimulated by the addition of 1.1-muM latex spheres as target particles for phagocytes, the dialysate of these cells exhibited greatly enhanced platelet-inhibitory properties. The addition of catalase to the platelets abolished the effect of exposing these cells to the dialysate of resting granulocytes and markedly inhibited the effect of exposing the platelets to the dialysate of phagocytosing granulocytes. Catalase treated with 3-amino-1,2,4-triazole had no platelet-protective capacity. Purified suspensions of lymphocytes released no platelet-inhibitory principle under these experimental conditions. Hydrogen peroxide in the dialysate of granulocytes was measured directly with an assay involving an H2O2-induced decrease in the fluorescence of scopoletin catalyzed by horseradish peroxidase. The dialysate of phagocytosing granulocytes contained 0.86 +/- 0.55 nmol H2O2/2.5 X 10(7) granulocytes when sampled at 20 min. By an alternate measurement technique in which scopoletin and horseradish peroxidase were present in the dialysate from time zero, the mean amount of H2O2 in the dialysate reached 4.0 +/- 1.3 nmol/2.5 x 10(7) granulocytes at 20 min. This discrepancy suggested the consumption of H2O2, possibly mediated by the granulocytes themselves. This possibility was investigated by the addition of exogenous H2O2 to the test system. Both granulocytes and platelets enhanced the disappearance of H2O2 from the dialysate, and the amount consumed was proportional to the amount of H2O2 added to the system. Glucose oxidase at 12 M U/ml plus glucose in excess resulted in the production of H2O2 at a rate and final amount comparable to that produced by phagocytosing granulocytes. This mixture, when substituted for phagocytosing granulocytes in the standard dialysis membrane experiment, induced an inhibition of platelet aggregation similar to that caused by the granulocytes. The observation that the release of H2O2 by the blood granulocyte influences platelet function suggests a potential role for the granulocyte in the regulation of hemostasis or thrombosis.

Adenosine Diphosphate↗
PubMed1989

Platelet receptor-mediated factor X activation by factor IXa. High-affinity factor IXa receptors induced by factor VIII are deficient on platelets in Scott syndrome.

We have studied factor IXa binding and factor X activation with normal platelets and with platelets obtained from a patient with a bleeding disorder and an isolated deficiency of platelet procoagulant activity termed Scott syndrome. In the absence of factor VIIIa and factor X, normal, thrombin-treated platelets exposed 560 +/- 35 sites for factor IXa with a Kd of 2.75 +/- 0.27 mM, compared with 461 +/- 60 sites per patient platelet with Kd of 3.2 +/- 0.33 nM. The addition of factor VIIIa and factor X resulted in a decrease in the Kd for normal platelets to 0.68 nM but had no effect on the Kd for patient platelets. The concentrations of factor IXa required for half-maximal rates of factor X activation for normal (0.52 nM) and patient platelets (2.5 nM) were similar to those determined from equilibrium binding studies. Kinetic parameters for factor X activation by factor IXa showed that the Km and Kcat were identical for normal and patient platelets in the absence of factor VIIIa. In the presence of factor VIIIa, and kcat for patient platelets (163 min-1) was only 33% of that for normal platelets (491 min-1): This result can be explained by the difference in affinity for factor IXa between normal and patient platelets in the presence of factor VIIIa, suggesting impaired factor VIIIa binding to Scott syndrome platelets.

Blood Coagulation Tests↗
PubMed1994

Detection of activated feline platelets in platelet-rich plasma by use of fluorescein-labeled antibodies and flow cytometry.

Platelets contribute to prethrombotic or thrombotic states; however, accepted evaluation methods (i.e., in vitro testing by use of an aggregometer) of platelet function in cats can be difficult because of the large volume of blood required from which platelets are isolated and the potential for platelet activation due to difficult venipunctures in sometimes uncooperative or excited animals. The activation problem also contributes to errors in platelet counts. Platelets from four domestic short haired cats (two males, two females, 2-3 years old) minimally restrained without sedation or anesthesia were evaluated. Blood (5 ml) was collected by jugular venipuncture directly into syringes containing 3.8% trisodium citrate (nine parts blood to one part anticoagulant) plus prostaglandin E1 (3 microM; 0.25, 0.5, 1, or 2 microliters/500 microliters citrate) or 3.8% trisodium citrate alone. Prostaglandin E1, which is a stable metabolite of arachidonic acid with platelet inhibitory properties similar to those of prostaglandin I2, was added to the anticoagulant to prevent activation of platelets during the collection process. Feline platelets exposed to prostaglandin E1 became immediately and persistently nonreactive to agonists, which negated their use in functional studies (aggregation, 14C-serotonin release, binding of fluorescein-conjugated antifibrinogen) but improved platelet counting accuracy. Detection of in vivo activation of platelets in prethrombotic and thrombotic states in humans has been done by identification of activation-dependent molecules on platelet surfaces by use of specific antibody recognition and detection by flow cytometric analysis. Many activation-dependent platelet surface receptor changes are species specific; however, fibrinogen appears to be conserved across species.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2001

Platelets from patients with the Quebec platelet disorder contain and secrete abnormal amounts of urokinase-type plasminogen activator.

The Quebec platelet disorder (QPD) is an autosomal dominant platelet disorder associated with delayed bleeding and alpha-granule protein degradation. The degradation of alpha-granule, but not plasma, fibrinogen in patients with the QPD led to the investigation of their platelets for a protease defect. Unlike normal platelets, QPD platelets contained large amounts of fibrinolytic serine proteases that had properties of plasminogen activators. Western blot analysis, zymography, and immunodepletion experiments indicated this was because QPD platelets contained large amounts of urokinase-type plasminogen activator (u-PA) within a secretory compartment. u-PA antigen was not increased in all QPD plasmas, whereas it was increased more than 100-fold in QPD platelets (P <.00009), which contained increased u-PA messenger RNA. Although QPD platelets contained 2-fold more plasminogen activator inhibitor 1 (PAI-1) (P <.0008) and 100-fold greater u-PA-PAI-1 complexes (P <.0002) than normal platelets, they contained excess u-PA activity, predominantly in the form of two chain (tcu-PA), which required additional PAI-1 for full inhibition. There was associated proteolysis of plasminogen in QPD platelets, to forms that comigrated with plasmin. When similar amounts of tcu-PA were incubated with normal platelet secretory proteins, many alpha-granule proteins were proteolyzed to forms that resembled degraded QPD platelet proteins. These data implicate u-PA in the pathogenesis of alpha-granule protein degradation in the QPD. Although patients with the QPD have normal to increased u-PA levels in their plasma, without evidence of systemic fibrinogenolysis, their increased platelet u-PA could contribute to bleeding by accelerating fibrinolysis within the hemostatic plug. QPD is the only inherited bleeding disorder in humans known to be associated with increased u-PA.

Blood Platelet Disorders↗
PubMed1988

Metabolism of platelet 5-hydroxytryptamine in acidified platelet concentrates.

The present study was designed to understand the metabolism of 5-hydroxytryptamine (serotonin, 5HT), a dense granule constituent of platelets, in acidified platelet concentrates (PC) during in vitro storage in polyvinylchloride plastic containers at 22 degrees C. High-performance liquid chromatographic analysis showed that significant amounts of 5HT and its metabolites, 5-hydroxytryptophol and 5-hydroxyindole-3-acetic acid (5HIAA), were detected in the plasma of all PC stored for 3 days with a pH below 6.0, measured at 37 degrees C. PC with a platelet number over 7 x 10(10) cells maintained low PO2 values. Rapid fall in pH occurred in these PC with low PO2 values. The rate of lactate production of platelets increased several fold because of an insufficient oxygen supply to them. In PC with a sufficient supply of oxygen, the adenosine triphosphate (ATP) production rates were estimated to be 8 nmol/min/10(9) platelets. In PC acidified below pH 6.0, the oxidative phosphorylation nearly ceased, and glycolysis was also inhibited: ATP production rates averaged 1 nmol/min/10(9) platelets at 3-day storage. Numerous clusters of platelet aggregates were found in acidified PC, and platelets changed into spherical shapes with accompanying swelling. These platelets did not respond to adenosine triphosphate and failed to produce shrinking when suspended in hypotonic solutions. 5HT was not metabolized in acidified platelet-poor plasma. These data suggest that the metabolic activity of platelets was impaired when the pH of the PC fell below 6.0, leading to the release of platelet 5HT into the plasma. A substantial amount of 5HT might be metabolized by platelet monoamine oxidase into 5HIAA and 5-hydroxytryptophol.

Blood Platelets↗
PubMed2003

Left atrial platelet activity with rheumatic mitral stenosis: correlation study of severity and platelet P-selectin expression by flow cytometry.

BACKGROUND: Previous studies have demonstrated that platelet activation, evaluated by measuring the secretory substances of platelets (ie, platelet factor 4 and beta-thromboglobulin), occurs in the peripheral blood of patients with rheumatic mitral stenosis (MS). However, the differences in platelet activation between peripheral and atrial blood, and the relationship between regional left atrial platelet P-selectin expression and the severity of MS have never been investigated. METHODS AND RESULTS: A total of 16 patients with symptomatic MS undergoing percutaneous transluminal mitral valvuloplasty were studied (group 1). The fractions of platelets expressing P selectin in the prevalvuloplasty left atrial, right atrial, peripheral venous, and arterial blood were determined by flow cytometry. The mitral valve area was calculated by means of the Doppler pressure half-time method. Peripheral venous platelet activity also was evaluated in 23 control patients (including 15 healthy volunteers who were in sinus rhythm [group 2] and 8 patients who had chronic lone atrial fibrillation [group 3]). The fraction of peripheral venous platelets expressing P selectin among group 1 patients was significantly higher than that of group 2 or 3 patients (p = 0.008). In group 1 patients, the fraction of platelets expressing P selectin in the left atrium was significantly higher than that in the right atrium, the femoral vein, or the femoral artery (p < 0.01). Correlation analysis demonstrated that there was a significantly direct relationship between the severity of MS and the fraction of left atrial platelets expressing P selectin (p = 0.01; r = -0.620). The fraction of peripheral venous platelets expressing P selectin among group 2 patients did not differ from that of group 3 patients CONCLUSIONS: In patients with rheumatic MS, increased regional left atrial platelet P-selectin expression had a significantly direct relationship with the severity of MS. The increased regional left atrial platelet P-selectin expression was not reflected in peripheral venous blood samples.

Adult↗
PubMed1989

Platelet-modified low density lipoprotein induces macrophage cholesterol accumulation and platelet activation.

Low density lipoprotein (LDL), modified by chemical or biological means, was shown to induce macrophage cholesterol accumulation. The cholesterol and protein contents of LDL were decreased (by 10 and 15%, respectively) by incubation of the LDL for 2 h at 37 degrees C with normal washed platelet suspension or with platelet-conditioned medium; these decreases were not affected by platelet activation. The platelet-modified LDL caused a greater increase (by up to 15%) in collagen-induced, in vitro platelet aggregation than control LDL. Incubation of mouse peritoneal macrophages with platelet-modified LDL for 18 h at 37 degrees C resulted in an elevation of the macrophage cholesterol ester content (by 35-50%) as well as an increase in the cholesterol esterification rate (by 40-70%), compared with the effect of control LDL. Macrophage cholesterol synthesis, however, was significantly decreased (by 40-50%), compared with the effect of control LDL. The effect of LDL treated by platelet-conditioned medium was similar to that of platelet-modified LDL. The effect of platelet-modified LDL on macrophage cholesterol esterification was maximal within 24 h of incubation, and it was not significantly affected by inhibition of cholesterol synthesis. The platelet-modified LDL was taken up by the macrophages in a saturable fashion and its uptake was competitively inhibited by LDL, but not by acetylated LDL. We conclude that platelet-modified LDL interacts with the LDL receptor and induces macrophage cholesterol accumulation. Since the modified lipoprotein induces in vitro foam cell formation and platelet activation, platelet-modified LDL could be considered to be pro-atherogenic.

Animals↗
PubMed2000

Platelet release of trimolecular complex components MT1-MMP/TIMP2/MMP2: involvement in MMP2 activation and platelet aggregation.

Matrix metalloproteinase 2 (MMP2) has been reported to be secreted by collagen-stimulated platelets, and active MMP2 has been shown to play a role in platelet aggregation. It has been demonstrated that MMP2 activation is dependent on the complex (membrane type 1 [MT1]-MMP/tissue inhibitor of MMP2 [TIMP2]) receptor and MMP2. We have investigated human platelets as a possible source of MT1-MMP, and we have studied its role in MMP2 activation and in platelet aggregation. Gelatin zymograms showed the existence of MMP2 at proforms (68 kd) and activated-enzyme forms (62-59 kd) in supernatants of resting and activated platelets, respectively. No gelatinolytic activity was associated with the platelet pellet after aggregation, suggesting a total release of MMP2 during cell activation. By Western blot analysis in nonreduced conditions, MT1-MMP was found on resting platelet membranes in 2 forms-the inactive 45-kd form and an apparent 89-kd form, which totally disappeared under reduced conditions. After platelet degranulation, only the 45-kd form was detected. Reverse transcription-polymerase chain reaction experiments showed the expression in platelets of messenger RNA encoding for MMP2, MT1-MMP, and TIMP2. Flow cytometry analysis showed that MT1-MMP, MMP2, and TIMP2 expressions were enhanced at the activated platelet surface. MMP inhibitors, recombinant TIMP2, and synthetic BB94 inhibited collagen-induced platelet aggregation in a concentration-dependent manner, indicating the role of activated MT1-MMP in the modulation of platelet function. In conclusion, our results demonstrate the expression of the trimolecular complex components (MT1-MMP/TIMP2/MMP2) by blood platelets as well as the ability of MMP inhibitors to modulate the aggregating response.

Blood Platelets↗
PubMed1989

Regulatory control of complement on blood platelets. Modulation of platelet procoagulant responses by a membrane inhibitor of the C5b-9 complex.

Antibody against a membrane inhibitor of the C5b-9 complex has been used to investigate regulatory control of the terminal complement proteins on blood platelets. Monospecific rabbit antibody (alpha-P18) was raised against the purified 18-kDa erythrocyte membrane inhibitor of C5b-9 (Sugita, Y., Nakano, Y., and Tomita, M. (1988) J. Biochem. (Tokyo) 104, 633-637). In addition to its interaction with erythrocytes, this antibody (and its Fab) bound specifically to platelet membranes. In immunoblots of cell membrane proteins prepared under non-reducing conditions, alpha-P18 bound specifically to an 18-kDa erythrocyte membrane protein and to a 37-kDa platelet membrane protein. Absorption of this antibody by platelet membranes competed its binding to the purified 18-kDa erythrocyte protein, suggesting that epitopes expressed by the erythrocyte 18-kDa C5b-9 inhibitor are common to the platelet. When bound to the platelet surface, the Fab of alpha-P18 increased C9 activation by membrane C5b-8, monitored by exposure of a complex-dependent C9 neo-epitope. Although alpha-P18 caused little increase in the cytolysis of platelets treated with C5b-9 (total release of lactate dehydrogenase less than 5%), it markedly increased the cell stimulatory responses induced by these complement proteins, including, secretion from platelet alpha- and dense granules, conformational activation of cell surface GP IIb-IIIa, release of membrane microparticles from the platelet surface, and exposure of new membrane binding sites for components of the prothrombinase enzyme complex. Prior incubation of C5b67 platelets with 100 micrograms/ml alpha-P18 (Fab) lowered by approximately 10-fold the half-maximal concentration of C8 required to elicit each of these responses (in the presence of excess C9). Incubation with alpha-P18 (Fab) alone did not activate platelets, nor did incubation with this antibody potentiate the stimulatory responses of platelets exposed to other agonists. These data indicate that a membrane inhibitor of the C5b-9 complex normally serves to attenuate the procoagulant responses of blood platelets exposed to activated complement proteins, and suggest the mechanism by which a deletion or inactivation of this cell surface component would increase the risk of vascular thrombosis.

Blood Platelets↗
PubMed1985

Agglutination of platelet-type von Willebrand's disease platelets by bovine von Willebrand factor.

It has been shown that platelets from patients with platelet-type von Willebrand's disease (vWD) agglutinate upon the addition of human von Willebrand factor (vWF) in the absence of ristocetin or botrocetin, suggesting that platelet membrane receptors for human vWF is abnormal. The present work reports the platelet agglutinability on stimulation with bovine vWF in platelet-type vWD. Platelets in patient platelet-rich plasma or washed platelet suspensions and patient platelets treated with formalin agglutinated in the presence of markedly lower concentrations of bovine vWF than those required for normal platelets. This finding provides additional evidence that platelet-type vWD platelets have abnormal expression of binding sites for vWF on their surface, and supports that platelet receptors for bovine vWF are identical or very close to those for human vWF.

Animals↗