Further Evidence that Glycoprotein IIb-IIIa Mediates Platelet Spreading on Subendothelium

1991 ◽  
Vol 65 (02) ◽  
pp. 202-205 ◽  
Author(s):  
Harvey J Weiss ◽  
Vincet T Turitto ◽  
Hans R Baumgartner
Keyword(s):  
Platelet Adhesion ◽  
Surface Coverage ◽  
Rabbit Aorta ◽  
Conclusive Evidence ◽  
Initial Contact ◽  
Single Exposure ◽  
Vessel Segment ◽  
Multiple Exposures ◽  
Wall Interaction ◽  
Platelet Spreading

SummaryIn order to explore further the mechanism by which glycoprotein GPIIb-IIIa promotes platelet vessel wall interaction, platelet adhesion to subendothelium was studied in an annular chamber in which subendothelium from rabbit aorta was exposed at a shear rate of 2,600 s−1 to blood from patients with thrombasthenia. Perfusions were conducted for each of 5 exposure times (1 ,2,3, 5 and 10 min), and the percent surface coverage of the vessel segment with platelets in the contact (C) and spread (S) stage was determined. Increased values of platelet contact (C) were obtained in thrombasthenia at all exposure times; this finding is consistent with a defect in platelet spreadirg, based on a previously described kinetic model of platelet attachment to subendothelium. According to this model of attachment, increased values of platelet contact (C) at a single exposure time may be indicative of either a defect in spreading (S) or initial contact (C), but multiple exposures will result in increased contact only for defects which are related to defectiye platelet spreading (s).The results obtained over a broad range of exposure times provide more conclusive evidence that GPIIb-IIIa mediates platelet spreading than those previously obtained at single exposure times.

scholarly journals Prostacyclin (prostaglandin I2, PGI2) inhibits platelet adhesion and thrombus formation on subendothelium

Blood ◽  
1979 ◽  
Vol 53 (2) ◽  
pp. 244-250 ◽  
Author(s):  
HJ Weiss ◽  
VT Turitto
Keyword(s):  
Blood Vessels ◽  
Human Blood ◽  
Platelet Adhesion ◽  
Platelet Rich Plasma ◽  
Thrombus Formation ◽  
Rabbit Aorta ◽  
Prostaglandin I2 ◽  
Shear Rates ◽  
Platelet Spreading ◽  
Aggregation Of Platelets

Abstract Prostaglandin I2 (prostacyclin, PGI2), a substance synthesized in the wall of blood vessels, has been previously shown to inhibit the aggregation of platelets in stirred platelet-rich plasma. We used a method in which segments of deendothelialized rabbit aorta are perfused at arterial shear rates with human blood and found that both platelet adhesion and thrombus formation on subendothelium was inhibited in blood containing 10 nM PGI2. PGI2 appears to reduce adhesion by inhibiting platelet spreading. These findings suggest that PGI2 could regulate the deposition of platelets on vascular surfaces.

scholarly journals Prostacyclin (prostaglandin I2, PGI2) inhibits platelet adhesion and thrombus formation on subendothelium

Blood ◽  
1979 ◽  
Vol 53 (2) ◽  
pp. 244-250 ◽  
Author(s):  
HJ Weiss ◽  
VT Turitto
Keyword(s):  
Blood Vessels ◽  
Human Blood ◽  
Platelet Adhesion ◽  
Platelet Rich Plasma ◽  
Thrombus Formation ◽  
Rabbit Aorta ◽  
Prostaglandin I2 ◽  
Shear Rates ◽  
Platelet Spreading ◽  
Aggregation Of Platelets

Prostaglandin I2 (prostacyclin, PGI2), a substance synthesized in the wall of blood vessels, has been previously shown to inhibit the aggregation of platelets in stirred platelet-rich plasma. We used a method in which segments of deendothelialized rabbit aorta are perfused at arterial shear rates with human blood and found that both platelet adhesion and thrombus formation on subendothelium was inhibited in blood containing 10 nM PGI2. PGI2 appears to reduce adhesion by inhibiting platelet spreading. These findings suggest that PGI2 could regulate the deposition of platelets on vascular surfaces.

Defective Platelet Adhesion and Aggregation on Subendothelium Exposed in Vivo or in Vitro to Flowing Blood of Fawn-Hooded Rats with Storage Pool Disease

1977 ◽  
Vol 38 (03) ◽  
pp. 0620-0629 ◽  
Author(s):  
Th. B Tschopp ◽  
H. R Baumgartner
Keyword(s):  
Platelet Adhesion ◽  
Surface Coverage ◽  
Thrombus Formation ◽  
Fibrillar Collagen ◽  
Rat Blood ◽  
Storage Pool ◽  
Platelet Thrombus ◽  
Platelet Spreading ◽  
Storage Pool Disease

SummaryCitrated rat blood was exposed to either subendothelium or the fibrillar collagen of enzymatically modified subendothelium of rabbit aorta in a perfusion system under laminar blood flow conditions at a wall shear rate of 830 s−1. The resulting platelet surface interaction was estimated by a morphometric method.With blood of fawn-hooded (FH) rats, which suffer from hereditary platelet “storage pool disease”, platelet spreading was slower on both exposed surfaces and resulted in a lower rate of surface coverage with platelets on subendothelium if compared with controls.The rate of adhesion of FH-platelets to the fibrillar collagen, however, was slightly higher as compared to controls despite reduced platelet spreading. This was probably due to the absence of platelet thrombus formation observed with FH-rat blood, whereas massive platelet thrombus formation took place in the controls. It is suggested that platelets of controls which arrive near the surface are preferentially incorporated into the rapidly forming platelet thrombi rather than reaching the surface, and hence do not increase surface-coverage with adhering platelets.The defective platelet adhesion and aggregation in the FH-rat was also apparent after desendothelialization of the aorta in vivo, although to a lesser extent, probably due to the extremely low thrombogenicity of rat aorta subendothelium.

Asialo von Willebrand Factor Enhances Platelet Adhesion to Vessel Subendothelium

1988 ◽  
Vol 60 (01) ◽  
pp. 030-034 ◽  
Author(s):  
Eva Bastida ◽  
Juan Monteagudo ◽  
Antonio Ordinas ◽  
Luigi De Marco ◽  
Ricardo Castillo
Keyword(s):  
Von Willebrand Factor ◽  
Platelet Adhesion ◽  
Human Albumin ◽  
Membrane Receptors ◽  
Shear Rates ◽  
High Shear Rates ◽  
Platelet Deposition ◽  
Platelet Spreading ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryNative von Willebrand factor (N-vWF) binds to platelets activated by thrombin, ADP or ristocetin. Asialo vWF (As-vWF) induces platelet aggregation in absence of platelet activators. N-vWF mediates platelet adhesion to vessel subendothelium at high shear rates. We have investigated the role of As-vWF in supporting platelet deposition to rabbit vessel subendothelium at a shear rate of 2,000 sec-1, using the Baumgartner perfusion system. We have studied the effects of the addition of As-vWF (from 2 to 12 μg/ml) to perfusates consisting of washed red blood cells, 4% human albumin and washed platelets. Our results show a significant increase in platelet deposition on subendothelium (p <0.01) in perfusions to which As-vWF had been added. Blockage of the platelet glycoproteins Ib and IIb/IIIa (GPIb and GPIIb/IIIa) by specific monoclonal antibodies (LJIb1 and LJCP8, respectively) resulted in a decrease of platelet deposition in both types of perfusates prepared with N-vWF and As-vWF. Our results indicate that As-vWF enhances platelet deposition to vessel subendothelium under flow conditions. Furthermore, they suggest that this effect is mediated by the binding of As-vWF to platelet membrane receptors, which in turn, promote platelet spreading and adhesion to the subendothelium.

scholarly journals Factor VIII/von Willebrand factor in subendothelium mediates platelet adhesion

Blood ◽  
1985 ◽  
Vol 65 (4) ◽  
pp. 823-831 ◽  
Author(s):  
VT Turitto ◽  
HJ Weiss ◽  
TS Zimmerman ◽  
II Sussman
Keyword(s):  
Factor Viii ◽  
Von Willebrand Factor ◽  
Vessel Wall ◽  
Platelet Adhesion ◽  
Human Factor ◽  
Rabbit Aorta ◽  
Human Factor Viii ◽  
Plasma Factor ◽  
Von Willebrand ◽  
Willebrand Factor

The present studies were undertaken to determine whether factor VIII/von Willebrand factor (vWF) present in the vessel wall (in addition to that in plasma) may mediate the attachment of platelets to subendothelium. Subendothelium from everted rabbit aorta was exposed to human citrated blood flowing through an annular perfusion chamber at 40 mL/min (wall shear rate of 2,600 s-1 for five minutes). The vessel segments were incubated at 37 degrees C for one hour with various dilutions of either goat-anti-rabbit factor VIII/vWF serum or an IgG fraction prepared from the serum. Control segments were incubated with serum or IgG from a nonimmunized goat. Values of platelet contact (C), platelet adhesion (C + S), and thrombus formation (T) on the subendothelium were evaluated by a morphometric technique. Compared with vessels incubated with fractions prepared from a normal goat, a significant decrease in platelet adhesion (C + S), ranging from 45% to 65%, was observed on vessels incubated with various dilutions (1:5 to 1:50) of either serum or IgG fractions of goat-anti-rabbit factor VIII/vWF. A similar decrease in platelet adhesion was observed with vessels incubated with an F(ab')2 fragment against rabbit factor VIII/vWF prepared in the goat. When goat-anti-rabbit factor VIII/vWF IgG was added to rabbit blood (1:75 dilution), platelet adhesion was reduced to the same extent (65%) on normal rabbit vessels and on vessels pre-incubated with goat-anti-rabbit factor VIII/vWF. Immunofluorescence studies revealed the presence of rabbit factor VIII/vWF in the subendothelium of rabbit aorta and the continued binding of the goat-anti-factor VIII/vWF antibodies on subendothelium during the perfusion studies. No uptake of human factor VIII/vWF on the rabbit subendothelium was observed by this immunologic technique; human factor VIII/vWF was found to be entirely associated with the attached human platelets. Thus, factor VIII/vWF in the vessel wall may mediate platelet attachment to subendothelium in a manner similar to that of plasma factor VIII/vWF.

scholarly journals Collagen-dependent platelet dysfunction and its relevance to either mitochondrial ROS or cytosolic superoxide generation: a question about the quality and functional competence of long-stored platelets

2020 ◽  
Author(s):  
Ehteramolsadat Hosseini ◽  
Saba Hojjati ◽  
Safoora Afzalniaye gashti ◽  
Mehran Ghasemzadeh
Keyword(s):  
Platelet Adhesion ◽  
Oxidant Stress ◽  
Ros Generation ◽  
Reverse Correlation ◽  
Platelet Dysfunction ◽  
Mitochondrial Ros ◽  
Ros Accumulation ◽  
The Matrix ◽  
Subendothelial Matrix ◽  
Platelet Spreading

Abstract Background: Upon vascular damage, the exposed subendothelial matrix recruits circulating platelets to site of injury while inducing their firm adhesion mainly via GPVI-collagen interaction. GPVI also supports aggregatory and pro-coagulant functions in arterial shear rate even on the matrix other than collagen. Reactive oxygen species (ROS) modulate these stages of thrombosis; however augmented oxidant stress also disturbs platelet functions. Stored-dependent platelet lesion is associated with the increasing levels of ROS. Whether ROS accumulation is also relevant to collagen-dependent platelet dysfunction is the main interest of this study. Methods: Fresh PRP-PCs (platelet concentrates) were either stimulated with potent ROS-inducers PMA and CCCP or stored for 5 days. Intra-platelet superoxide (O2--) or mitochondrial-ROS and GPVI expression were detected by flowcytometery. GPVI shedding, platelet aggregation and spreading/adhesion to collagen were analyzed by western blot, aggregometry and fluorescence-microscopy respectively. Results: Mitochondrial-ROS levels in 5 days-stored PCs were comparable to those induced by mitochondrial uncoupler, CCCP while O2-- generations were higher than those achieved by PMA. Shedding levels in 5 days-stored PCs were higher than those induced by these potent stimuli. GPVI expressions were reduced comparably in CCCP treated and 5 days-stored PCs. Platelet adhesion was also diminished during storage while demonstrating significant reverse correlation with GPVI shedding. However, only firm adhesion (indicated by spreading or platelet adhesion surface area) was relevant to GPVI expression. Platelet adhesion and aggregation also showed reverse correlations with both O2-- and mitochondrial-ROS formations; nonetheless mitochondrial-ROS was only relevant to firm adhesion. Conclusion: As a sensitive indicator of platelet activation, GPVI shedding correlated with either simple adhesion or spreading to collagen, while GPVI expression was only relevant to platelet spreading. Thereby, if the aim of GPVI evaluation is to examine platelet firm adhesion, expression seems to be a more specific choice. Furthermore, the comparable levels of ROS generation in 5 days-stored PCs and CCCP treated platelets, indicated that these products are significantly affected by oxidative stress. Reverse correlation of accumulating ROS with collagen-dependent platelet dysfunction is also a striking sign of an oxidant-induced lesion that may raise serious question about the post-transfusion quality and competence of longer stored products.

scholarly journals The role of Akt in the signaling pathway of the glycoprotein Ib-IX–induced platelet activation

Blood ◽  
2008 ◽  
Vol 111 (2) ◽  
pp. 658-665 ◽  
Author(s):  
Hong Yin ◽  
Aleksandra Stojanovic ◽  
Nissim Hay ◽  
Xiaoping Du
Keyword(s):  
Signaling Pathway ◽  
Platelet Adhesion ◽  
Adenosine Diphosphate ◽  
Human Platelets ◽  
Integrin Activation ◽  
Akt Inhibitor ◽  
Glycoprotein Ib ◽  
Platelet Spreading ◽  
Von Willebrand ◽  
Inside Out

The platelet von Willebrand factor (vWF) receptor, glycoprotein Ib-IX (GPIb-IX), mediates platelet adhesion and induces signaling leading to integrin activation. Phosphoinositol 3-kinase (PI3K) is important in GPIb-IX–mediated signaling. PI3K–dependent signaling mechanisms, however, are unclear. We show that GPIb-IX–induced platelet aggregation and stable adhesion under flow were impaired in mouse platelets deficient in PI3K effectors, Akt1 and Akt2, and in human platelets treated with an Akt inhibitor, SH-6. Akt1 and Akt2 play important roles in early GPIb-IX signaling independent of Syk, adenosine diphosphate (ADP), or thromboxane A2 (TXA2), in addition to their recognized roles in ADP- and TXA2–dependent secondary amplification pathways. Knockout of Akt1 or Akt2 diminished platelet spreading on vWF but not on immobilized fibrinogen. Thus, Akt1 and Akt2 are both required only in the GPIb-IX–mediated integrin activation (inside-out signaling). In contrast, PI3K inhibitors abolished platelet spreading on both vWF and fibrinogen, indicating a role for PI3K in integrin outside-in signaling distinct from that in GPIb-IX–mediated inside-out signaling. Furthermore, Akt1- or Akt2-deficiency diminished vWF–induced cGMP elevation, and their inhibitory effects on GPIb-IX–dependent platelet adhesion were reversed by exogenous cGMP. Thus, Akt1 and Akt2 mediate GPIb-IX signaling via the cGMP–dependent signaling pathway.

Histochemical and Ultrastructural study of the Platelet-Arterial Subendothelium Interaction

1979 ◽  
Author(s):  
Y.J. Legrand ◽  
J. Bariety ◽  
P. Birembaut ◽  
H. Michel ◽  
F. Fauvel ◽  
...  
Keyword(s):  
Tannic Acid ◽  
Platelet Adhesion ◽  
Ricinus Communis ◽  
Blood Perfusion ◽  
Rabbit Aorta ◽  
Human Platelets ◽  
Ruthenium Red ◽  
Ultrastructural Studies ◽  
Bacterial Collagenase ◽  
Before And After

In order to characterize the subendothelial macromolecules able to interact with platelets rabbit aortas were de-endothelialized and incubated either with chymotrypsin (24 h at 37° C), with a highly purified bacterial collagenase (2 h at 37° C), or with chymotrypsin followed by collagenase or the reverse. Histochemical ultrastructural studies were performed before and after blood perfusion, using three different staining procedures: tannic acid (for the microfibrillar structures and elastin), ruthenium red (for the polyanions) and two peroxidase-labelled lectins (concanavalin A and ricinus communis (for the detection of saccharidic determinants)). After chymotrypsin, the tannic acid +ve, ruthenium red +ve and lectin +ve microfibrils had been digested; platelet adherence to the remaining sparse collagen fibrils persisted. After collagenase, these microfibrils are preserved, collagen has been digested, but the platelets can still adhere. After combined incubation with both enzymes, elastin is the only remaining constituent and no platelet adhesion can be observed.These results show that in the rabbit aorta subendothelium besides collagen, microfibrillar glycoproteins are able to interact with human platelets.

Untangling the cultural component behind the contextual placement of out-of-home advertising

2019 ◽  
Vol 61 (5) ◽  
pp. 502-517
Author(s):  
Mirahmad Amirshahi ◽  
Samira Jafari Dizicheh ◽  
Rick T Wilson
Keyword(s):  
Cognitive Processing ◽  
Exposure Condition ◽  
Multiple Exposure ◽  
Single Exposure ◽  
Experimental Conditions ◽  
High Involvement ◽  
Brand Evaluations ◽  
Multiple Exposures ◽  
Culturally Based ◽  
Cultural Component

Companies frequently place out-of-home advertisements in locations hoping their brand becomes associated with that environment’s favorable attributes. However, prior research using U.S. subjects suggested that these associative benefits do not actually transfer onto the advertised brand. We faithfully replicate this earlier research using a non-Western sample and find that culturally based communication and cognitive processing models may explain the lack of results in the earlier study and affirmative results in our study. Three experimental conditions are used: single exposure, multiple exposures, and high involvement. We find that a billboard’s external environment does influence brand evaluations but only in the single-exposure condition. A possible explanation for why results were not evident in the multiple exposure and high involvement conditions may be related to the amount of message elaboration across study conditions.

scholarly journals Thrombospondin inhibits adhesion of platelets to glass and protein- covered substrata

Blood ◽  
1988 ◽  
Vol 71 (4) ◽  
pp. 1096-1099 ◽  
Author(s):  
J Lahav
Keyword(s):  
Platelet Adhesion ◽  
Binding Capacity ◽  
Inhibitory Effect ◽  
Adsorbed Protein ◽  
Platelet Binding ◽  
Platelet Spreading ◽  
Glass Surfaces ◽  
Adhesion Of Platelets

Abstract Glass and protein-covered surfaces when treated with the platelet- secreted glycoprotein thrombospondin lose their capacity to bind unstimulated platelets. In comparison to the number that bind to fibronectin-covered glass surfaces, less than 3% bind to thrombospondin- covered glass surfaces. When the fibronectin-covered surface is incubated with thrombospondin, it loses 87% of its binding capacity for platelets. The inhibitory effect of thrombospondin on platelet binding increases with increasing amounts of the adsorbed protein and reaches maximal values at 65% saturation of the adsorption of thrombospondin to the surface. Platelet spreading on the surface is also completely inhibited by thrombospondin. These data suggest that thrombospondin is nonthrombogenic and can modulate platelet adhesion to the subendothelium.

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