Lipid rafts are critical membrane domains in blood platelet activation processes

INSERM U563, Centre de Physiophatologie Toulouse Purpan, Département d'Oncogenèse et signalisation dans les cellules hématopoi
Biochimica et Biophysica Acta (Impact Factor: 4.66). 04/2003; 1610(2):247-57. DOI: 10.1016/S0005-2736(03)00022-1
Source: PubMed


Among the various hematopoi;etic cells, platelets are critical for maintaining the integrity of the vascular system. They must be rapidly activated by sequential and coordinated mechanisms in order to efficiently prevent haemorrhage upon vascular injury. Several signal transduction pathways lead to platelet activation in vitro and in vivo, among them, several are initiated via receptors or co-receptors containing immuno-receptor tyrosine-based activation motifs (ITAM) which trigger downstream signalling like the immune receptors in lymphocytes. However, in contrast to immune cells for which the role of lipid rafts in signalling has largely been described, the involvement of laterally segregated membrane microdomains in platelet activation has been investigated only recently. The results obtained until now strongly suggest that early steps of platelet activation via the collagen receptor GpVI or via FcgammaRIIa occur preferentially in these microdomains where specific proteins efficiently organize key downstream signalling pathways. In addition, lipid rafts also contribute to platelet activation via heterotrimeric G-protein-coupled receptors. They are sites where the phosphoinositide (PI) metabolism is highly active, leading to a local generation of lipid second messengers such as phosphatidylinositol 3,4,5-trisphosphate. Here, evidence is accumulating that cholesterol-enriched membrane microdomains are part of a general process that contributes to the efficiency and the coordination of platelet activation mechanisms. Here we will discuss the biochemical and functional characterizations of human platelet rafts and their potential impact in platelet physiopathology.

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Available from: Stéphane Bodin, Apr 09, 2015
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    • "As in our case, spherical or near spherical MPs have been observed previously and recent analysis using atomic force microscopy also appears to confirm these characteristics [32]. The average size observed in our experiments appears in agreement with the observation that MPs may be derived from internal bodies of the platelets or from lipid rafts [33] as recent studies focusing on the detection and isolation methods of vesicles are also reporting [34,35,36]. "
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    ABSTRACT: With the objective of making advancements in the area of pro-thrombotic microparticle characterization in cardiovascular biology, we present a novel method to separate blood circulating microparticles using a membrane-based, nanopore filtration system. In this qualitative study, electron microscopy observations of these pro-thrombotic mouse microparticles, as well as mouse platelets and leukocytes obtained using a mouse inferior vena cava ligation model of deep-vein thrombosis are presented. In particular, we present mouse microparticle morphology and microstructure using SEM and TEM indicating that they appear to be mostly spherical with diameters in the 100 to 350 nm range. The nanopore filtration technique presented is focused on the development of novel methodologies to isolate and characterize blood circulating microparticles that can be used in conjunction with other methodologies. We believe that determination of microparticle size and structure is a critical step for the development of reliable assays with clinical or research application in thrombosis and it will contribute to the field of nanomedicine in thrombosis.
    12/2011; 2(1):1-15. DOI:10.3390/membranes2010001
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    • "Platelet functions were investigated in many respects. Blending time, percentage of aggregation platelet, ultrastructural evaluation of platelets [1] [23] were investigated, as well as the composition and organization of the platelet membrane lipid [9] [24] [25], and the interaction between platelet membrane components [26-28] and drugs [29]. The interaction between proteins and lipids was observed by negative staining electron microscopy [26], capillary electrophoresis with laser-induced fluorescence detection [30] and Surface Plasmon Resonance [31] [32]. "
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    ABSTRACT: Abciximab (Abci) and eptifibatide (Epti) are antiaggregate drugs which may reduce thrombotic complications in acute coronary syndromes. The aim of this work was the investigation of the interaction between the phospholipid-GPIIb/IIIa glycoprotein complex and Abci or Epti, and the influence of these drugs on the phospholipid ratio in the platelet membrane. The interaction between the phospholipid-GPIIb/IIIa glycoprotein complex and antiaggregate drugs were investigated using the Surface Plasmon Resonance Imaging technique (SPRI). Phospholipids phosphatidylinositol (PI), phosphatidylserine (PS), phosphatidylethanolamine (PE), phosphatidylcholine (PC) and sphingomyelin (SM) were first immobilized onto the gold chip surface. The phospholipid ratio in the platelet membrane was determined by the HPLC. Only PI, PS, PE and PC were determined. Human platelets treated 'in vitro' with Abci or Epti exhibit changes in the phospholipid ratio in the platelet membrane. The ratio of PS decreases and PC rises. The SPRI distinctly shows interactions between phospholipids and glycoprotein GPIIb/IIIa, and between the phospholipid-glycoprotein GPIIb/IIIa complex and Abci or Epti. The interaction between phospholipids and glycoprotein GPIIb/IIIa is growing in the sequence: PI<SM<PE<PC<PS. The interaction between phospholipid-glycoprotein GPIIb/IIIa complex and Abci/Epti is growing in the sequence: PS<PI<PC<PE<SM. SPRI was proved to be excellent tool for observation of such interactions.
    Folia Histochemica et Cytobiologica 12/2010; 48(4):687-92. DOI:10.2478/v10042-010-0090-3 · 1.36 Impact Factor
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    • "We next investigated whether ERβ was resident within the lipid rafts of the platelet membrane. Recent reports have described different experimental protocols as suitable to isolate lipid rafts from human platelets, using either 0.1% Brij58 or 0.1% Triton X-100 [20] [35]. In preliminary experiments, upon platelet lysis with Brij58, we found that GM1 ganglioside, a positive marker for membrane lipid rafts, was recovered in less Fig. 1. "
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    ABSTRACT: The impact of estrogens on the viability of cardiovascular system and their ability to regulate platelet function is still an open and debated question. We have previously shown that estrogen is able to significantly potentiate the aggregation induced by low doses of thrombin and to initiate a rapid and reversible signaling pathway mediated by ERbeta-directed activation of the tyrosine kinases Src and Pyk2 at the level of the plasma membrane. Lipid rafts are critical, cholesterol-enriched membrane domains, which play a major role in blood platelet activation processes. In this work, we investigated the role of lipid rafts in 17beta-estradiol signaling in human platelets. We observed that membrane rafts were essential for both 17beta-estradiol-dependent potentiation of platelet aggregation induced by subthreshold concentrations of thrombin and 17beta-estradiol-induced phosphorylation of Src. 17beta-estradiol caused the reversible translocation of ERbeta to the raft fractions and promoted the rapid and transient recruitment to, and activation within the membrane raft domains of the tyrosine kinases Src and Pyk2. The raft integrity was essential with this respect, as these effects of 17beta-estradiol were completely inhibited by cholesterol depletion. This paper provides evidence for the first time that membrane lipid rafts coordinate estrogen signaling in human platelets.
    Biochimica et Biophysica Acta 03/2007; 1773(2):273-8. DOI:10.1016/j.bbamcr.2006.12.001 · 4.66 Impact Factor
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