Platelet integrins and immunoreceptors

Kasirer-Friede, Ana; Kahn, Mark L.; Shattil, Sanford J.

doi:10.1111/j.1600-065x.2007.00532.x

Cited by 122 publications

(104 citation statements)

References 275 publications

(291 reference statements)

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“…1 Recent observations suggest that α IIb β 3 is also involved in proplatelet formation. 2,3 Integrin α IIb β 3 function depends on two different signal transduction pathways: inside-out and outside-in signaling.…”

Section: Cytoskeletal Perturbation Leads To Platelet Dysfunction and mentioning

confidence: 99%

Cytoskeletal perturbation leads to platelet dysfunction and thrombocytopenia in variant forms of Glanzmann thrombasthenia

et al. 2015

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Several patients have been reported to have variant dominant forms of Glanzmann thrombasthenia, associated with macrothrombocytopenia and caused by gain-of-function mutations of ITGB3 or ITGA2B leading to reduced surface expression and constitutive activation of integrin α IIb β 3 . The mechanisms leading to a bleeding phenotype of these patients have never been addressed. The aim of this study was to unravel the mechanism by which ITGB3 mutations causing activation of α IIb β 3 lead to platelet dysfunction and macrothrombocytopenia. Using platelets from two patients carrying the β 3 del647-686 mutation and Chinese hamster ovary cells expressing different α IIb β 3 -activating mutations, we showed that reduced surface expression of α IIb β 3 is due to receptor internalization. Moreover, we demonstrated that permanent triggering of α IIb β 3 -mediated outside-in signaling causes an impairment of cytoskeletal reorganization arresting actin turnover at the stage of polymerization. The induction of actin polymerization by jasplakinolide, a natural toxin that promotes actin nucleation and prevents depolymerization of stress fibers, in control platelets produced an impairment of platelet function similar to that of patients with variant forms of dominant Glanzmann thrombasthenia. del647-686β 3 -transduced murine megakaryocytes generated proplatelets with a reduced number of large tips and asymmetric barbell-proplatelets, suggesting that impaired cytoskeletal rearrangement is the cause of macrothrombocytopenia. These data show that impaired cytoskeletal remodeling caused by a constitutively activated α IIb β 3 is the main effector of platelet dysfunction and macrothrombocytopenia, and thus of bleeding, in variant forms of dominant Glanzmann thrombasthenia. Cytoskeletal perturbation leads to platelet dysfunction and thrombocytopenia in variant forms of Glanzmann thrombasthenia

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Section: Cytoskeletal Perturbation Leads To Platelet Dysfunction and mentioning

confidence: 99%

Cytoskeletal perturbation leads to platelet dysfunction and thrombocytopenia in variant forms of Glanzmann thrombasthenia

et al. 2015

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“…The subendothelial matrixprotein collagen mainly binds to the immunoglobulin receptor glycoprotein VI (GPVI), which via the src kinase family members Lyn and Fyn phosphorylates the immunoreceptor tyrosine-based activation motif (ITAM) of the cytoplasmic tail of the FcR -chain, followed by the recruitment of the spleen tyrosine kinase (Syk) which in turn phosphorylates the linker for activation of T cells (LAT), finally funneling into the activation of phospholipase C isoform 2 (PLC2) [14]. As collagen may activate other platelet receptors besides GPVI, we applied within our study the snake venom toxin convulxin, a highly selective GPVI agonist [15].…”

Section: Introductionmentioning

confidence: 99%

The Toll-like receptor 2/1 (TLR2/1) complex initiates human platelet activation via the src/Syk/LAT/PLCγ2 signalling cascade

Fälker

Klarström-Engström

Bengtsson

et al. 2014

Cellular Signalling

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“…Members of this family are 1) GPVI, the major receptor for collagen, 2) FcγRIIA (CD32), a single-chain sialoglycoprotein, involves in calcium signalling and cytoskeletal rearrangement, platelets secretion and activation, 3) FcεRI receptors (CD23), the "low-affinity" receptor for IgE, which seems to act as a bridge between aggregation and immunity [35,36].…”

Section: The Traditional Role Of Platelets In the Haemostasis Processmentioning

confidence: 99%

The Two Faces of Thrombosis: Coagulation Cascade and Platelet Aggregation. Are Platelets the Main Therapeutic Target?

Cimmino¹,

Fischetti²,

Golino³

2017

J Thrombo Cir

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Acute thrombus formation is the pathophysiological substrate underlying several clinical conditions, such as acute coronary syndrome (ACS) and stroke. Activation of coagulation cascade is a key step of the thrombotic process: vessel injury results in exposure of the glycoprotein tissue factor (TF) to the flowing blood. Once exposed, TF binds factor VII/VIIa (FVII/FVIIa) and in presence of calcium ions, it forms a tertiary complex able to activate FX to FXa, FIX to FIXa, and FVIIa itself. The final step is thrombin formation at the site of vessel injury with subsequent platelet activation, fibrinogen to fibrin conversion and ultimately thrombus formation.Platelets are the key cells in primary hemostasis. For years they have been considered only as cell fragments participating to primary hemostasis and onto which coagulation factors are assembled in the process of thrombus formation. However, recent advances in platelets pathophysiology have shown that these cells are able to regulate their gene and protein expression, make de novo protein synthesis, and release different mediators with paracrine effects that may interfere with different cell functions.Pharmacological modulation of both side of thrombosis, coagulation cascade and platelet activation, is of great clinical importance. Several clinical trials have clearly shown the efficacy of anticoagulation and/or anti platelet aggregation in different thrombotic disorders. This article aims at reviewing the recent advancements on the two faces of thrombosis focusing on the emerging role of platelets not only as clot-forming components, but highlighting their involvement in the inflammatory-immune system, as well as in modulation of different cell functions.

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Platelet integrins and immunoreceptors

Cited by 122 publications

References 275 publications

Cytoskeletal perturbation leads to platelet dysfunction and thrombocytopenia in variant forms of Glanzmann thrombasthenia

Cytoskeletal perturbation leads to platelet dysfunction and thrombocytopenia in variant forms of Glanzmann thrombasthenia

The Toll-like receptor 2/1 (TLR2/1) complex initiates human platelet activation via the src/Syk/LAT/PLCγ2 signalling cascade

The Two Faces of Thrombosis: Coagulation Cascade and Platelet Aggregation. Are Platelets the Main Therapeutic Target?

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