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Small GTPases 2021Platelets are master regulators and effectors of haemostasis with increasingly recognized functions as mediators of inflammation and immune responses. The Rho family of... (Review)
Review
Platelets are master regulators and effectors of haemostasis with increasingly recognized functions as mediators of inflammation and immune responses. The Rho family of GTPase members Rac1, Cdc42 and RhoA are known to be major components of the intracellular signalling network critical to platelet shape change and morphological dynamics, thus playing a major role in platelet spreading, secretion and thrombus formation. Initially linked to the regulation of actomyosin contraction and lamellipodia formation, recent reports have uncovered non-canonical functions of platelet RhoGTPases in the regulation of reactive oxygen species (ROS), where intrinsically generated ROS modulate platelet function and contribute to thrombus formation. Platelet RhoGTPases orchestrate oxidative processes and cytoskeletal rearrangement in an interconnected manner to regulate intracellular signalling networks underlying platelet activity and thrombus formation. Herein we review our current knowledge of the regulation of platelet ROS generation by RhoGTPases and their relationship with platelet cytoskeletal reorganization, activation and function.
Topics: Animals; Blood Platelet Disorders; Blood Platelets; Humans; Reactive Oxygen Species; rho GTP-Binding Proteins
PubMed: 33459160
DOI: 10.1080/21541248.2021.1878001 -
Journal of Thrombosis and Haemostasis :... Nov 2016Essentials Platelets play an important role in pathogen recognition. Platelets contain several complement factors and can interact with E. coli. Platelet's complement...
UNLABELLED
Essentials Platelets play an important role in pathogen recognition. Platelets contain several complement factors and can interact with E. coli. Platelet's complement protein C3 differs from plasmatic C3 in its electrophoretic mobility. Upon contact with bacteria, platelets are activated and can enhance complement activation.
SUMMARY
Background The role of platelets in immune defense is increasingly being recognized. Platelets bind complement proteins from plasma, initiate complement activation, and interact with bacteria. However, the contribution of platelets to complement-mediated defense against bacterial infections is not known in detail. Objectives To assess platelet interactions with Escherichia coli strains, and evaluate the contributions of platelet complement proteins to host defense. Methods We studied the cell-cell interactions of a pathogenic and a non-pathogenic E. coli strain with platelet concentrates, washed platelets and manually isolated platelets by flow cytometry and ELISA. The presence of complement proteins and complement RNA in megakaryocytes and platelets was analyzed by PCR, RT-PCR, confocal microscopy, and western blotting. Results Incubation with E. coli leads to platelet activation, as indicated by the expression of CD62P and CD63 on the platelet surface. RNA and protein analyses show that megakaryocytes and platelets contain complement C3, and that platelet C3 migrates differently on polyacrylamide gels than plasmatic C3. Activation of platelets by bacteria leads to translocation of C3 to the cell surface. This translocation is not induced by thrombin receptor activating peptide or lipopolysaccharide. Interaction of platelets with E. coli occurs even in the absence of plasma proteins, and is independent of platelet toll-like receptor 4 and α β (glycoprotein IIbIIIa). Conclusion Platelets contain a specific form of C3. Importantly, they can modulate immune defense against bacteria by enhancing plasmatic complement activation.
Topics: Blood Platelets; Cell Membrane; Cell Separation; Complement Activation; Complement C3; Escherichia coli; Escherichia coli Infections; Fetal Blood; Flow Cytometry; Humans; Immune System; Immunity, Innate; Megakaryocytes; P-Selectin; Platelet Activation; Platelet Glycoprotein GPIIb-IIIa Complex; Tetraspanin 30; Toll-Like Receptor 4
PubMed: 27590476
DOI: 10.1111/jth.13495 -
International Journal of Molecular... Aug 2017Platelets play a fundamental role in normal hemostasis, while their inherited or acquired dysfunctions are involved in a variety of bleeding disorders or thrombotic... (Review)
Review
Platelets play a fundamental role in normal hemostasis, while their inherited or acquired dysfunctions are involved in a variety of bleeding disorders or thrombotic events. Several laboratory methodologies or point-of-care testing methods are currently available for clinical and experimental settings. These methods describe different aspects of platelet function based on platelet aggregation, platelet adhesion, the viscoelastic properties during clot formation, the evaluation of thromboxane metabolism or certain flow cytometry techniques. Platelet aggregometry is applied in different clinical settings as monitoring response to antiplatelet therapies, the assessment of perioperative bleeding risk, the diagnosis of inherited bleeding disorders or in transfusion medicine. The rationale for platelet function-driven antiplatelet therapy was based on the result of several studies on patients undergoing percutaneous coronary intervention (PCI), where an association between high platelet reactivity despite P2Y12 inhibition and ischemic events as stent thrombosis or cardiovascular death was found. However, recent large scale randomized, controlled trials have consistently failed to demonstrate a benefit of personalised antiplatelet therapy based on platelet function testing.
Topics: Blood Platelets; Humans; Platelet Adhesiveness; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Reproducibility of Results; Sensitivity and Specificity; Thrombosis; Ticlopidine
PubMed: 28820484
DOI: 10.3390/ijms18081803 -
The Netherlands Journal of Medicine Jun 2010Upon vessel wall injury platelets rapidly adhere to the exposed subendothelial matrix which is mediated by several cellular receptors present on platelets or endothelial... (Review)
Review
Upon vessel wall injury platelets rapidly adhere to the exposed subendothelial matrix which is mediated by several cellular receptors present on platelets or endothelial cells and various adhesive proteins such as von Willebrand factor, collagen and fibrinogen. Subsequent platelet activation results in the recruitment of additional platelets and the generation of platelet aggregates forming a stable platelet plug. In addition, activated platelets form a strong link between primary and secondary haemostasis as they provide the phospholipid surface that is necessary for the assembly of activated coagulation factor complexes required for thrombin generation. Other than the physiological function acting as a first line of defence against bleeding, platelets may also contribute to pathological thrombus formation. Platelets play an important role in thromboembolic diseases and may contribute to the formation of occlusive thrombi which can lead to severe complications such as stroke or myocardial infarction. Improved understanding of the respective roles of the various cellular receptors, adhesive proteins and regulatory proteins involved in platelet-vessel wall interaction and subsequent thrombus formation, both under physiological and pathological conditions, has led to the development and investigation of a broad range of antiplatelet drugs. This review provides an overview of the current knowledge on the mechanisms involved in the interaction between platelets and vascular endothelium and discusses recent advancements in the development of drugs interfering with platelet-vessel wall interaction at various stages of thrombus formation.
Topics: Blood Platelets; Blood Vessels; Humans; Platelet Adhesiveness; Platelet Aggregation; Thrombosis
PubMed: 20558854
DOI: No ID Found -
International Journal of Molecular... Jul 2021Platelets are hematopoietic cells whose main function has for a long time been considered to be the maintenance of vascular integrity. They have an essential role in the... (Review)
Review
Platelets are hematopoietic cells whose main function has for a long time been considered to be the maintenance of vascular integrity. They have an essential role in the hemostatic response, but they also have functional capabilities that go far beyond it. This review will provide an overview of platelet functions. Indeed, stress signals may induce platelet apoptosis through proapoptotis or hemostasis receptors, necrosis, and even autophagy. Platelets also interact with immune cells and modulate immune responses in terms of activation, maturation, recruitment and cytokine secretion. This review will also show that platelets, thanks to their wide range of innate immune receptors, and in particular toll-like receptors, and can be considered sentinels actively participating in the immuno-surveillance of the body. We will discuss the diversity of platelet responses following the engagement of these receptors as well as the signaling pathways involved. Finally, we will show that while platelets contribute significantly, via their TLRs, to immune response and inflammation, these receptors also participate in the pathophysiological processes associated with various pathogens and diseases, including cancer and atherosclerosis.
Topics: Animals; Atherosclerosis; Blood Platelets; Humans; Immunity, Innate; Neoplasms; Platelet Activation; Receptors, Immunologic; Toll-Like Receptors
PubMed: 34360659
DOI: 10.3390/ijms22157894 -
Molecular Medicine Reports Jan 2021Platelets are small pieces of cytoplasm that have become detached from the cytoplasm of mature megakaryocytes (MKs) in the bone marrow. Platelets modulate vascular... (Review)
Review
Platelets are small pieces of cytoplasm that have become detached from the cytoplasm of mature megakaryocytes (MKs) in the bone marrow. Platelets modulate vascular system integrity and serve important role, particularly in hemostasis. With the rapid development of clinical medicine, the demand for platelet transfusion as a life‑saving intervention increases continuously. Stem cell technology appears to be highly promising for transfusion medicine, and the generation of platelets from stem cells would be of great value in the clinical setting. Furthermore, several studies have been undertaken to investigate the potential of producing platelets from stem cells. Initial success has been achieved in terms of the yields and function of platelets generated from stem cells. However, the requirements of clinical practice remain unmet. The aim of the present review was to focus on several sources of stem cells and factors that induce MK differentiation. Updated information on current research into the genetic regulation of megakaryocytopoiesis and platelet generation was summarized. Additionally, advanced strategies of platelet generation were reviewed and the progress made in this field was discussed.
Topics: Blood Platelets; Cell Culture Techniques; Cell Differentiation; Culture Media; Gene Expression Regulation; Humans; Stem Cells; Thrombopoiesis
PubMed: 33179095
DOI: 10.3892/mmr.2020.11645 -
Platelets Jul 2020Electron microscopy has been a valuable tool for the study of platelet biology and thrombosis for more than 70 years. Early studies using conventional transmission and... (Review)
Review
Electron microscopy has been a valuable tool for the study of platelet biology and thrombosis for more than 70 years. Early studies using conventional transmission and scanning electron microscopy (EM) provided a foundation for our initial understanding of platelet structure and how it changes upon platelet activation. EM approaches have since been utilized to study platelets and thrombi in the context of basic, translational and clinical research, and they are instrumental in the diagnosis of multiple platelet function disorders. In this brief review, we provide a sampling of the many contributions EM based studies have made to the field, including both historical highlights and contemporary applications. We will also discuss exciting new imaging modalities based on EM and their utility for the study of platelets, hemostasis and thrombosis into the future.
Topics: Blood Platelets; Hemostasis; Humans; Microscopy, Electron; Thrombosis
PubMed: 32423268
DOI: 10.1080/09537104.2020.1763939 -
International Journal of Molecular... Nov 2019Human pregnancy relies on hemochorial placentation, including implantation of the blastocyst and deep invasion of fetal trophoblast cells into maternal uterine blood... (Review)
Review
Human pregnancy relies on hemochorial placentation, including implantation of the blastocyst and deep invasion of fetal trophoblast cells into maternal uterine blood vessels, enabling direct contact of maternal blood with placental villi. Hemochorial placentation requires fast and reliable hemostasis to guarantee survival of the mother, but also for the neonates. During human pregnancy, maternal platelet count decreases gradually from first, to second, and third trimester. In addition to hemodilution, accelerated platelet sequestration and consumption in the placental circulation may contribute to a decline of platelet count throughout gestation. Local stasis, turbulences, or damage of the syncytiotrophoblast layer can activate maternal platelets within the placental intervillous space and result in formation of fibrin-type fibrinoid. Perivillous fibrinoid is a regular constituent of the normal placenta which is considered to be an important regulator of intervillous hemodynamics, as well as having a role in shaping the developing villous trees. However, exaggerated activation of platelets at the maternal-fetal interface can provoke inflammasome activation in the placental trophoblast, and enhance formation of circulating platelet-monocyte aggregates, resulting in sterile inflammation of the placenta and a systemic inflammatory response in the mother. Hence, the degree of activation determines whether maternal platelets are a friend or foe of the human placenta. Exaggerated activation of maternal platelets can either directly cause or propagate the disease process in placenta-associated pregnancy pathologies, such as preeclampsia.
Topics: Blood Platelets; Female; Hemostasis; Humans; Placenta; Placentation; Pre-Eclampsia; Pregnancy
PubMed: 31718032
DOI: 10.3390/ijms20225639 -
Blood Transfusion = Trasfusione Del... May 2021The impact of donor biology on blood component storability is increasingly appreciated as a determinant of the storage lesion and post-transfusion performances. Platelet...
BACKGROUND
The impact of donor biology on blood component storability is increasingly appreciated as a determinant of the storage lesion and post-transfusion performances. Platelet metabolism is affected by age and it is critical to platelet responses to activating stimuli in an age-dependent manner. Sex has been previously highlighted as a contributing factor to the platelet proteomics lesion. However, little is known about the impact of donor sex and age on stored platelet metabolism and post-transfusion capacity to circulate.
MATERIALS AND METHODS
Apheresis platelets were donated via apheresis by 21 healthy volunteers (12 males and 9 females; ages 20 to 59). Metabolomics analyses were performed at day 0 and after 5 days of storage at 22+2 °C, along with autologous post-transfusion recovery and survival studies with Cr and In.
RESULTS
Sex and age significantly impacted platelet metabolism at baseline and upon storage. Platelets from older, male donors were characterised by higher levels of Krebs cycle metabolites, pentose phosphate pathway intermediates and byproducts, deaminated purines and long chain fatty acids. These metabolites ranked amongst the top significant correlates to post-transfusion recoveries. Glutathione homeostasis and sphingosine 1-phosphate were the top positive correlates to long term survival, which was lower in platelets from older, male donors - without reaching statistical significance.
DISCUSSION
In this study we report that donor sex and age have a significant impact on platelet metabolism. Novel metabolic correlates to platelet post-transfusion performances (24 h recovery and long-term survival) were identified through high-resolution, stable isotope-labeled internal standard-assisted metabolomics approach.
Topics: Adult; Blood Donors; Blood Platelets; Blood Preservation; Female; Humans; Male; Middle Aged; Platelet Function Tests; Platelet Transfusion; Young Adult
PubMed: 33085601
DOI: 10.2450/2020.0145-20 -
Blood Jun 2021Platelets are critical for hemostasis and thrombosis, but recent research highlights their role in many other processes, including inflammation, wound healing, and...
Platelets are critical for hemostasis and thrombosis, but recent research highlights their role in many other processes, including inflammation, wound healing, and lymphangiogenesis. Edited by José López, this series focuses on the emerging role of platelets in cancer, influencing tumor growth and metastasis, immune evasion, and tumor angiogenesis. The reviews present the current understanding of mutual cross talk between platelets and tumors, communication mediated by RNA transfer and extracellular vesicles, and the potential of antiplatelet agents for cancer treatment.
Topics: Blood Platelets; Humans; Neoplasms; Platelet Activation
PubMed: 33940613
DOI: 10.1182/blood.2020010237