The central role of the P
                            2T
                        
 receptor in amplification of human platelet activation, aggregation, secretion and procoagulant activity

SummaryThe aim of this study was to determine if there is a correlation between the activity of a MoAb as an agonist and its ability to bind to the Fc platelet receptor, FcγRIIa. A polymorphism at amino acid 131 [arginine (Arg) or histidine (His)] of FcγRIIa was first shown to be determinant for MoAb-IgG1 binding on monocytes. To clarify the role of this polymorphism in platelet activation by MoAb-IgG1 we (i) established the FCγRIIA polymorphism at the gene level by adapting the denaturating gradient gel electrophoresis method, (ii) analyzed the binding affinity of the MoAbs to FrγRIIa on platelets from homozygous Arg, homozygous His, and heterozygous Arg/His donors, and (iii) characterized the different reactivities of platelets according to the FCγRIIA polymorphism. Among 167 Caucasian donors we found 46% heterozygous Arg/His, 36% homozygous His and 18% homozygous Arg. ALB6, an anti CD9, P256 an anti GPIIb-IIIa, and AP3 an anti-GPIIIa were chosen according to their ability (ALB6, P256) or not (AP3) to activate platelets. These 3 MoAbs-IgG1 bind to FcγRIIa with a stronger affinity for the Arg-form of FcγRIIa, a result which was confirmed with the use of diverse MoAbs directed against various antigens. The different abilities of MoAbs to bind to the two FcγRIIa forms were well correlated to the different platelet responses induced by ALB6 and P256. However, low concentrations of ALB6, which allow full activation of platelets from homozygous Arg donors, as did P256, did not induce any activation of platelets from homozygous His donors, whereas P256 is able to induce a low aggregation. The results further define the respective roles of the antigen and the Fc receptor, depending on the MoAb, and the role of the FcγRIIa polymorphism in platelet activation induced by MoAbs. In addition, the results obtained with MoAbs unable to induce platelet activation provide evidence that the binding of a MoAb on FcγRIIa does not predict its ability to activate platelets.

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Role of Caspase in a Subset of Human Platelet Activation Responses

Blood ◽

10.1182/blood.v93.12.4222 ◽

1999 ◽

Vol 93 (12) ◽

pp. 4222-4231 ◽

Cited By ~ 119

Author(s):

Anna Shcherbina ◽

Eileen Remold-O’Donnell

Keyword(s):

Platelet Activation ◽

Caspase 3 ◽

Human Platelet ◽

Thrombus Formation ◽

Shape Change ◽

Vascular Wall ◽

Human Platelets ◽

Granule Secretion ◽

Platelets Function

Abstract Platelets function to protect the integrity of the vascular wall. A subset of platelet activation responses that are especially important for thrombus formation include exposure of phosphatidylserine and release of microparticles, which generate procoagulant surfaces. The resemblance of these platelet activation processes to events occurring in nucleated cells undergoing apoptosis suggests a possible role for caspases, which are major effector enzymes of nucleated cell apoptosis. We demonstrate here the presence of caspase-3 in human platelets and its activation by physiological platelet agonists. Using cell-permeable specific inhibitors, we demonstrate a role for a caspase-3–like protease in the agonist-induced (collagen plus thrombin or Ca2+ ionophore) platelet activation events of phosphatidylserine exposure, microparticle release, and cleavage of moesin, a cytoskeletal-membrane linker protein. The role of caspase-3 in platelet activation is restricted rather than global, because other activation responses,  granule secretion, shape change, and aggregation were unaffected by caspase-3 inhibitors. Experiments with two classes of protease inhibitors show that caspase-3 function is distinct from that of calpain, which is also involved in late platelet activation events. These findings show novel functions of caspase and provide new insights for understanding of platelet activation.

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Role of arachidonic acid metabolism in human platelet activation and irreversible aggregation

American Journal of Hematology ◽

10.1002/ajh.2830190404 ◽

1985 ◽

Vol 19 (4) ◽

pp. 339-347 ◽

Cited By ~ 19

Author(s):

Gundu H. R. Rao ◽

James G. White

Keyword(s):

Arachidonic Acid ◽

Platelet Activation ◽

Acid Metabolism ◽

Human Platelet ◽

Arachidonic Acid Metabolism ◽

Irreversible Aggregation

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The role of extracellular Ca2+ and Na+ in paf-acether-induced human platelet activation

Biochemical Pharmacology ◽

10.1016/0006-2952(89)90109-3 ◽

1989 ◽

Vol 38 (20) ◽

pp. 3415-3421 ◽

Cited By ~ 1

Author(s):

Chantal Lalau Keraly ◽

Daniele Delautier ◽

Jacques Benveniste

Keyword(s):

Platelet Activation ◽

Human Platelet

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Investigations of human platelet-type 12-lipoxygenase: role of lipoxygenase products in platelet activation

The Journal of Lipid Research ◽

10.1194/jlr.m026385 ◽

2012 ◽

Vol 53 (12) ◽

pp. 2546-2559 ◽

Cited By ~ 50

Author(s):

Kenneth N. Ikei ◽

Jennifer Yeung ◽

Patrick L. Apopa ◽

Jesús Ceja ◽

Joanne Vesci ◽

...

Keyword(s):

Platelet Activation ◽

Human Platelet ◽

Lipoxygenase Products ◽

12 Lipoxygenase

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Role of Caspase in a Subset of Human Platelet Activation Responses

Blood ◽

10.1182/blood.v93.12.4222.412k34_4222_4231 ◽

1999 ◽

Vol 93 (12) ◽

pp. 4222-4231 ◽

Cited By ~ 2

Author(s):

Anna Shcherbina ◽

Eileen Remold-O’Donnell

Keyword(s):

Platelet Activation ◽

Caspase 3 ◽

Human Platelet ◽

Thrombus Formation ◽

Shape Change ◽

Vascular Wall ◽

Human Platelets ◽

Granule Secretion ◽

Platelets Function

Platelets function to protect the integrity of the vascular wall. A subset of platelet activation responses that are especially important for thrombus formation include exposure of phosphatidylserine and release of microparticles, which generate procoagulant surfaces. The resemblance of these platelet activation processes to events occurring in nucleated cells undergoing apoptosis suggests a possible role for caspases, which are major effector enzymes of nucleated cell apoptosis. We demonstrate here the presence of caspase-3 in human platelets and its activation by physiological platelet agonists. Using cell-permeable specific inhibitors, we demonstrate a role for a caspase-3–like protease in the agonist-induced (collagen plus thrombin or Ca2+ ionophore) platelet activation events of phosphatidylserine exposure, microparticle release, and cleavage of moesin, a cytoskeletal-membrane linker protein. The role of caspase-3 in platelet activation is restricted rather than global, because other activation responses,  granule secretion, shape change, and aggregation were unaffected by caspase-3 inhibitors. Experiments with two classes of protease inhibitors show that caspase-3 function is distinct from that of calpain, which is also involved in late platelet activation events. These findings show novel functions of caspase and provide new insights for understanding of platelet activation.

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