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Brian R Smith - One of the best experts on this subject based on the ideXlab platform.

  • aspirin does not inhibit adenosine diphosphate induced Platelet alpha granule release
    Blood, 1993
    Co-Authors: Christine S Rinder, Henry M Rinder, J L Bonan, L A Student, Brian R Smith
    Abstract:

    The involvement of metabolites of arachidonic acid in Platelet-dense granule secretion and secondary Platelet-Platelet interactions is well characterized. However, their role in heterotypic interactions dependent on Alpha-Granule secretion is less well understood. Using Platelet-surface expression of P-selectin as a marker of Alpha-Granule secretion, we have shown that: (1) aspirin treatment of Platelets at doses that block dense granule secretion does not inhibit Alpha-Granule secretion to adenosine diphosphate (ADP); (2) synergism between epinephrine and ADP in the induction of P-selectin expression is similarly unaffected by aspirin; and (3) the ability of P-selectin to mediate adhesion of activated Platelets to monocytes and polymorphonuclear lymphocytes in whole blood is also unchanged by aspirin treatment. To further explore the mechanisms responsible for Platelet Alpha-Granule secretion, we have shown that inhibition of Na+/H+ exchange by either acidification of the extracellular medium or amiloride treatment blocked ADP-induced P-selectin expression. In contrast, incubation with the Platelet lipoxygenase inhibitor 5,8,11- eicosatrynoic acid, by itself and with aspirin, did not decrease ADP- induced P-selectin expression. We conclude that Platelet Alpha-Granule secretion in response to ADP is dependent on intact Na+/H+ exchange but is independent of the lipoxygenase- and cyclooxygenase-dependent metabolites of arachidonic acid.

  • activation in stored Platelet concentrates correlation between membrane expression of p selectin glycoprotein iib iiia and beta thromboglobulin release
    Transfusion, 1993
    Co-Authors: Henry M Rinder, Edward L Snyder, J L Bonan, P Napychank, H Malkus, Brian R Smith
    Abstract:

    By using two distinct measurements of alpha-degranulation (surface P-selectin [Alpha-Granule membrane protein-140] expression and beta-thromboglobulin [beta-TG] release) and quantitation of glycoprotein (GP) IIb/IIIa surface density, stored Platelet concentrates were evaluated to determine a) which method of measuring Platelet Alpha-Granule release was more sensitive in detecting early Platelet activation; b) whether Day 1 levels of activation predicted the extent of activation or cell lysis on Day 5 of storage; and c) whether changes in surface GPIIb/IIIa density were primarily dependent on Platelet activation. By using samples from paired and unpaired units stored for 1, 3, and 5 days, four observations could be made. 1) A flow cytometric assay for the percentage of P-selectin-positive Platelets was more sensitive for early detection of Platelet activation than was measurement of beta-TG release. This finding was most likely due to enhanced sensitivity in detecting Platelets that had undergone partial Alpha-Granule release. 2) Total P-selectin expression correlated with beta-TG release, which indicated that the extent of Alpha-Granule membrane fusion with the external Platelet membrane was proportional to the amount of Alpha-Granule contents released into the supernatant. 3) All of the activation measurements on Day 1 predicted the activation values, but did not predict the degree of cell lysis (measured by lactate dehydrogenase discharge), on Day 5 of storage. 4) Surface GPIIb/IIIa density was increased on the subset of P-selectin-positive Platelets as compared with the P-selectin-negative subset at all times during storage, but, within each subset, GPIIb/IIIa surface density did not significantly increase over the time of storage.

Amos Panet - One of the best experts on this subject based on the ideXlab platform.

  • selective inhibition of Platelet macroaggregate formation by a recombinant heparin binding domain of human thrombospondin
    Arteriosclerosis Thrombosis and Vascular Biology, 1994
    Co-Authors: Chantal Legrand, Veronica Morandi, Simona Mendelovitz, Hadassa Shaked, Jacob Hartman, Amos Panet
    Abstract:

    Thrombospondin (TSP) is a Platelet Alpha-Granule adhesive protein that plays a critical role in the stabilization of thrombus by promoting the formation of Platelet macroaggregates. We have recently shown that a monoclonal antibody (mAb) to the NH2-terminal heparin-binding domain of TSP, MAII, inhibits Platelet aggregation induced by thrombin in a dose-dependent manner. In this study, we have expressed in Escherichia coli two recombinant proteins comprising residues 1 to 174 (TSP18) and 1 to 242 (TSP28) of TSP. After purification, both proteins reacted equally well with mAb MAII, whereas the reactivity of TSP18 for heparin was lower than that of TSP28 or native TSP. At micromolar concentrations, TSP18 and TSP28 inhibited the second wave of Platelet aggregation and the concomitant release of [14C]5-hydroxytryptamine induced by ADP in citrated Platelet-rich plasma as well as aggregation and secretion induced by a low concentration of thrombin in washed Platelet suspensions. The proteins did not inhibit surface expression of endogenous TSP on activated Platelets, as measured by the binding of radiolabeled mAb 5G11, indicating that they did not interfere with the primary binding of TSP to the plasma membrane. In contrast, in a solid-phase binding assay, the proteins inhibited in a dose-dependent manner (IC50, 0.1 and 0.06 mumol/L for TSP18 and TSP28, respectively) the binding of radiolabeled TSP to surface-adsorbed fibrinogen. Furthermore, specific and saturable binding of the proteins to immobilized fibrinogen was demonstrated by enzyme-linked immunosorbent assay. The results suggest that interaction between the heparin-binding domain of TSP and membrane-bound fibrinogen may be critical in the Platelet aggregation/secretion process.

Henry M Rinder - One of the best experts on this subject based on the ideXlab platform.

  • aspirin does not inhibit adenosine diphosphate induced Platelet alpha granule release
    Blood, 1993
    Co-Authors: Christine S Rinder, Henry M Rinder, J L Bonan, L A Student, Brian R Smith
    Abstract:

    The involvement of metabolites of arachidonic acid in Platelet-dense granule secretion and secondary Platelet-Platelet interactions is well characterized. However, their role in heterotypic interactions dependent on Alpha-Granule secretion is less well understood. Using Platelet-surface expression of P-selectin as a marker of Alpha-Granule secretion, we have shown that: (1) aspirin treatment of Platelets at doses that block dense granule secretion does not inhibit Alpha-Granule secretion to adenosine diphosphate (ADP); (2) synergism between epinephrine and ADP in the induction of P-selectin expression is similarly unaffected by aspirin; and (3) the ability of P-selectin to mediate adhesion of activated Platelets to monocytes and polymorphonuclear lymphocytes in whole blood is also unchanged by aspirin treatment. To further explore the mechanisms responsible for Platelet Alpha-Granule secretion, we have shown that inhibition of Na+/H+ exchange by either acidification of the extracellular medium or amiloride treatment blocked ADP-induced P-selectin expression. In contrast, incubation with the Platelet lipoxygenase inhibitor 5,8,11- eicosatrynoic acid, by itself and with aspirin, did not decrease ADP- induced P-selectin expression. We conclude that Platelet Alpha-Granule secretion in response to ADP is dependent on intact Na+/H+ exchange but is independent of the lipoxygenase- and cyclooxygenase-dependent metabolites of arachidonic acid.

  • activation in stored Platelet concentrates correlation between membrane expression of p selectin glycoprotein iib iiia and beta thromboglobulin release
    Transfusion, 1993
    Co-Authors: Henry M Rinder, Edward L Snyder, J L Bonan, P Napychank, H Malkus, Brian R Smith
    Abstract:

    By using two distinct measurements of alpha-degranulation (surface P-selectin [Alpha-Granule membrane protein-140] expression and beta-thromboglobulin [beta-TG] release) and quantitation of glycoprotein (GP) IIb/IIIa surface density, stored Platelet concentrates were evaluated to determine a) which method of measuring Platelet Alpha-Granule release was more sensitive in detecting early Platelet activation; b) whether Day 1 levels of activation predicted the extent of activation or cell lysis on Day 5 of storage; and c) whether changes in surface GPIIb/IIIa density were primarily dependent on Platelet activation. By using samples from paired and unpaired units stored for 1, 3, and 5 days, four observations could be made. 1) A flow cytometric assay for the percentage of P-selectin-positive Platelets was more sensitive for early detection of Platelet activation than was measurement of beta-TG release. This finding was most likely due to enhanced sensitivity in detecting Platelets that had undergone partial Alpha-Granule release. 2) Total P-selectin expression correlated with beta-TG release, which indicated that the extent of Alpha-Granule membrane fusion with the external Platelet membrane was proportional to the amount of Alpha-Granule contents released into the supernatant. 3) All of the activation measurements on Day 1 predicted the activation values, but did not predict the degree of cell lysis (measured by lactate dehydrogenase discharge), on Day 5 of storage. 4) Surface GPIIb/IIIa density was increased on the subset of P-selectin-positive Platelets as compared with the P-selectin-negative subset at all times during storage, but, within each subset, GPIIb/IIIa surface density did not significantly increase over the time of storage.

J Rhartman - One of the best experts on this subject based on the ideXlab platform.

  • selective inhibition of Platelet macroaggregate formation by a recombinant heparin binding domain of human thrombospondin
    Arteriosclerosis and Thrombosis: A Journal of Vascular Biology, 1994
    Co-Authors: J Rhartman
    Abstract:

    Thrombospondin (TSP) is a Platelet Alpha-Granule adhesive protein that plays a critical role in the stabilization of thrombus by promoting the formation of Platelet macroaggregates. We have recently shown that a monoclonal antibody (mAb) to the NH2-terminal heparin-binding domain of TSP, MAII, inhibits Platelet aggregation induced by thrombin in a dose-dependent manner. In this study, we have expressed in Escherichia coli two recombinant proteins comprising residues 1 to 174 (TSP18) and 1 to 242 (TSP28) of TSP. After purification, both proteins reacted equally well with mAb MAII, whereas the reactivity of TSP18 for heparin was lower than that of TSP28 or native TSP. At micromolar concentrations, TSP18 and TSP28 inhibited the second wave of Platelet aggregation and the concomitant release of [14C]5-hydroxytryptamine induced by ADP in citrated Platelet-rich plasma as well as aggregation and secretion induced by a low concentration of thrombin in washed Platelet suspensions. The proteins did not inhibit surf...

J L Bonan - One of the best experts on this subject based on the ideXlab platform.

  • aspirin does not inhibit adenosine diphosphate induced Platelet alpha granule release
    Blood, 1993
    Co-Authors: Christine S Rinder, Henry M Rinder, J L Bonan, L A Student, Brian R Smith
    Abstract:

    The involvement of metabolites of arachidonic acid in Platelet-dense granule secretion and secondary Platelet-Platelet interactions is well characterized. However, their role in heterotypic interactions dependent on Alpha-Granule secretion is less well understood. Using Platelet-surface expression of P-selectin as a marker of Alpha-Granule secretion, we have shown that: (1) aspirin treatment of Platelets at doses that block dense granule secretion does not inhibit Alpha-Granule secretion to adenosine diphosphate (ADP); (2) synergism between epinephrine and ADP in the induction of P-selectin expression is similarly unaffected by aspirin; and (3) the ability of P-selectin to mediate adhesion of activated Platelets to monocytes and polymorphonuclear lymphocytes in whole blood is also unchanged by aspirin treatment. To further explore the mechanisms responsible for Platelet Alpha-Granule secretion, we have shown that inhibition of Na+/H+ exchange by either acidification of the extracellular medium or amiloride treatment blocked ADP-induced P-selectin expression. In contrast, incubation with the Platelet lipoxygenase inhibitor 5,8,11- eicosatrynoic acid, by itself and with aspirin, did not decrease ADP- induced P-selectin expression. We conclude that Platelet Alpha-Granule secretion in response to ADP is dependent on intact Na+/H+ exchange but is independent of the lipoxygenase- and cyclooxygenase-dependent metabolites of arachidonic acid.

  • activation in stored Platelet concentrates correlation between membrane expression of p selectin glycoprotein iib iiia and beta thromboglobulin release
    Transfusion, 1993
    Co-Authors: Henry M Rinder, Edward L Snyder, J L Bonan, P Napychank, H Malkus, Brian R Smith
    Abstract:

    By using two distinct measurements of alpha-degranulation (surface P-selectin [Alpha-Granule membrane protein-140] expression and beta-thromboglobulin [beta-TG] release) and quantitation of glycoprotein (GP) IIb/IIIa surface density, stored Platelet concentrates were evaluated to determine a) which method of measuring Platelet Alpha-Granule release was more sensitive in detecting early Platelet activation; b) whether Day 1 levels of activation predicted the extent of activation or cell lysis on Day 5 of storage; and c) whether changes in surface GPIIb/IIIa density were primarily dependent on Platelet activation. By using samples from paired and unpaired units stored for 1, 3, and 5 days, four observations could be made. 1) A flow cytometric assay for the percentage of P-selectin-positive Platelets was more sensitive for early detection of Platelet activation than was measurement of beta-TG release. This finding was most likely due to enhanced sensitivity in detecting Platelets that had undergone partial Alpha-Granule release. 2) Total P-selectin expression correlated with beta-TG release, which indicated that the extent of Alpha-Granule membrane fusion with the external Platelet membrane was proportional to the amount of Alpha-Granule contents released into the supernatant. 3) All of the activation measurements on Day 1 predicted the activation values, but did not predict the degree of cell lysis (measured by lactate dehydrogenase discharge), on Day 5 of storage. 4) Surface GPIIb/IIIa density was increased on the subset of P-selectin-positive Platelets as compared with the P-selectin-negative subset at all times during storage, but, within each subset, GPIIb/IIIa surface density did not significantly increase over the time of storage.