摘要:

Cell-cell and cell-extracellular matrix interactions are mediated by a number of membrane glycoproteins. On the basis of structural homologies, several families of cell adhesion molecules (integrins, selectins, immunoglobulins, cadherins, leucine-rich glycoproteins) have been established. Since 1991, a new family of CD36-like proteins has been identified. CD36 is a cell surface glycoprotein that interacts with a large variety of ligands. CD36 has been implicated in thrombosis, vascular biology, lipid metabolism and atherogenesis. In this review, we aim to summarize our present knowledge on this important, multifunctional glycoprotein.

ISSN:0953-7104    

DOI:10.3109/09537109609023570

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Two papers published in this journal1,2during the past year remind us that plasma albumin concentrations can influence platelet function. These publications, together with epidemiological evidence showing that low plasma concentrations of albumin predict mortality from cardiovascular disease3,4have prompted this review.

ISSN:0953-7104    

DOI:10.3109/09537109609023571

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

There is controversy in the literature regarding the effects of plasmin on human platelets. We have studied the effects of plasmin on platelet glycoproteins, aggregation, shape change and secretion and found them to be dependent on experimental conditions: (a) Plasmin's effects on human platelets are only seen in gel-filtered platelets (GFP), presumably because in platelet rich plasma plasmin is bound to a2-antiplasmin; (b) in GFP to which fibrinogen has been added, platelet function remains intact; and (c) in the absence of fibrinogen, the effect of plasmin on GFP depends on whether stirring is performed or not. With stirring, platelets undergo shape change, secretion and aggregation in response to added plasmin. Aggregation is much stronger when CaClz1 mM is added. Without stirring, preincubation of GFP with plasmin leads to inhibition of platelet aggregation induced by subsequent platelet stimuli (thrombin, collagen, ristocetin or U46619). We have demonstrated that plasmin is a true platelet activating agent, in the sense that it induces platelet shape change and secretion. Plasmin will induce aggregation when added to stirred GFP. This may be because stirring protects glycoprotein (GP) IIbIIIa bound fibrinogen from being degradated by plasmin. When added to unstirred GFP, GP IIbIIIa bound fibrinogen may be readily accessible to degradation by plasmin, which may then behave like a platelet inhibitor.

ISSN:0953-7104    

DOI:10.3109/09537109609023572

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Non-steroidal anti-inflammatory drugs (NSAID) are frequently prescribed but gastrointestinal haemorrhages and inhibition of platelet function are two side effects that limit their use. Nabumetone belongs to a new prostaglandin-sparing class of NSAID with a low potential for causing gastrointestinal mucosal irritancy and inhibition of platelet function.We have used flow cytometry andin vitrobleeding time (IVBT) to measure the effects of nabumetone on platelet function in healthy volunteers. Nabumetone was found to cause a significant decrease in platelet-bound fibrinogen after adenosine diphosphate (ADP) activation using flow cytometry and a significant increase in IVBT when using CaCl2as activating substance. The platelet inhibitory effect was less pronounced than the changes seen with low dose aspirin. Flow cytometry and IVBT are two sensitive methods well suited for clinical use and could both be used to monitor drug-induced inhibition of platelet function.

ISSN:0953-7104    

DOI:10.3109/09537109609023573

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Endotoxin (lipopolysaccharide, LPS) is a major component of the outermost membrane of gram-negative bacteria. Endotoxin is an important mediator of septic shock and it is involved in the development of disseminated intravascular coagulation (DIC), which is a dreaded complication of gram-negative bacterial infections. Platelet microvesicles are platelet derived vesicles that are formed during platelet activation. These microvesicles are too small to be detected by cell counters used in clinical laboratories, but they are active in haemostasis and may thus contribute to the development of DIC. We have used flow cytometry to study thein vivoeffect of endotoxin on platelet microvesicle formation in clinical material and in a porcine model. We found increased levels of platelet microvesicles in patients with gram-negative bacterial sepsis. Endotoxin infusion in pigs caused microvesicle formation of up to four times the initial value. Thus, the formation of such microvesicles, which are associated with increased coagulation activity, may be initiated by endotoxin.

ISSN:0953-7104    

DOI:10.3109/09537109609023574

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Platelet activation by adenosine diphosphate (ADP) results in changes in the composition of the large cytoskeletal fragments that can be isolated following solubilization of platelets with Triton X-100 and low speed centrifugation. Here we have used several different agents that modify platelet responses to investigate some of the factors that affect these cytoskeletal changes. All the experiments involved use of hirudinized platelet-rich plasma in which TXA, synthesis and release of dense body constituents does not occur following platelet activation with ADP. ADP alone caused a significant and sustained increase in the cytoskeletal content of actin binding protein (ABP), myosin,α-actinin, a 66K protein and actin, and a significant decrease in a 31K protein. In the presence of MK-852 or GR 144053 (GpIIbDIIa antagonists), in samples merely left unstirred and in Glanzmann's thrombasthesenia, ADP produced no increase in ABP or the 66K protein and no decrease in the 31K protein. The increase in myosin andα-actinin became reversible but there was still incorporation of actin into the cytoskeleton. In the presence of ARL 66096 (a P2Tpurinoceptor antagonist that inhibits aggregation but not shape change) there was no increase in ABP or the 66K protein and no decrease in the 31K protein. ARL 66096 also prevented incorporation ofα-actinin and actin. As with MK-852, myosin incorporation became reversible. Iloprost inhibited all the cytoskeletal changes, the effects of MgCI2were similar to those of MK-852, and acetylsalicylic acid (ASA) had no effect. In some experiments MK-852, ARL 66096, iloprost or MgCI, were added 0.5 min after the ADP. They all produced disaggregation and this was accompanied by reversal of the changes in the composition of the cytoskeleton that had occurred initially on stimulating the platelets with ADP. The results suggest that: (1) myosin is incorporated into the cytoskeleton transiently during shape change; (2) ADP interaction with the P2Treceptor leads to incorporation ofα-actinin and actin into the cytoskeleton as well as platelet aggregation; (3) further incorporation ofα-actinin and myosin and incorporation of ABP and the 66K protein occur consequent to fibrinogen binding and platelet aggregation; (4) displacement of the 31K protein from the cytoskeleton is also a consequence of fibrinogen binding and platelet aggregation; (5) platelet disaggregation is accompanied by reversal of any cytoskeletal changes that have already occurred; (6) continuous occupation of the P2Treceptor is required for maintenance of the cytoskeletal changes; (7) CAMP inhibits and reverses cytoskeletal assembly; and (8) MgCl2acts similarly to a GpIIb/IIIa antagonist under these experimental conditions.

ISSN:0953-7104    

DOI:10.3109/09537109609023575

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

P-selectin (PADGEM protein, GMP-140 or CD 62) is a glycoprotein of platelet a-granules and endothelial Weibel-Palade bodies that, by mediating cellular adhesion, initiates recruitment of leukocytes and lymphocytes into injured tissue. Both of the endothelial antiplatelet autacoids prostacyclin (PGI2) and nitric oxide (NO) have been demonstrated to inhibit P-selectin expression. Prostaglandin endoperoxides PGG2/PGH2that are generated by activated platelets have been demonstrated to be used by endothelium for generation of prostacyclin. In an experimental modelin vitrothat resembles vessel wall/platelet/PMN interactionin vivo, we found that aspirin (100μM), a COX inhibitor, but not L-NMMA (100μM) and a NO-synthase inhibitor, reversed the inhibitory effect of arterial wall on P-selectin mediated platelet/PMN adhesion. The anti-adhesive potency of vessel wall reversed by aspirin was dose-dependently restored by camonagrel (3-100μM), a new TXA2synthase inhibitor. We conclude that selective TXA2-synthase inhibitors may inhibit P-selectin mediated platelet/PMN adhesion by augmenting formation of prostacyclin by vessel walls.

ISSN:0953-7104    

DOI:10.3109/09537109609023576

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

In diabetic patients, where the membrane lipid microviscosity of blood platelets is altered, the availability of platelet membrane receptors may change concomitantly. Platelet hypersensitivity in diabetic subjects was previously hypothesized to result from the nonenzymatic glycosylation-induced loss in platelet membrane fluidity. In our present study juvenile type 1 diabetic subjects were compared with their relevant controls with respect to thrombin-stimulated platelet activation in relation to glycation-induced impairments of platelet membrane dynamics. Our results indicate that: (a) the mean steady-state fluorescence polarization (p) of both 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-anilino-8-naphthalenesulphonate (ANS) in membranes from diabetic subjects were significantly greater than for control subjects, thus indicating reduced membrane lipid fluidity in diabetic platelets in various membrane regions; (b) the significantly higher [3H]NaBH4reduction, indicating the increased attachment of glucose to protein amino groups, was attributed to the proteins extracted from diabetic platelet membranes; (c) CD62-positive resting platelets were not significantly more abundant in diabetic patients; (d) basically, unaltered amounts of PADGEM-140 membrane antigen (CD62) copies were detected in resting diabetic platelets; (e) significantly higher numbers of membrane glycoproteinβ3were found in diabetic platelets; (f) thrombin-induced elevations in the expression of CD61 (β3) and CD62 (PADGEM-140) occurred to much higher extent in platelets of diabetic patients, thus pointing to more profound activation of diabetic platelets by thrombin; (g) the total amounts of platelet membrane glycoproteinβ3was significantly reduced in platelet lysates from diabetic subjects. We conclude that glycation-induced rigidization of platelet membranes might hypersensitize diabetic platelets to aggregating agents by rendering platelet membrane receptors more exposed to the external environment. Thus, thrombin may bind more efficiently to the exposed glycoprotein receptors (due to glycation) in diabetic platelets. Such excessive exposure and displacements toward the external environment might favour the accelerated shedding of some membrane proteins in diabetic platelets. We further suggest that their subsequent replacements would render platelet intrinsic storage pools exhausted and thus, might explain the diminished total amount ofβ3found in platelets of diabetic patients.

ISSN:0953-7104    

DOI:10.3109/09537109609023577

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor