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Cells Nov 2022In addition to their role in haemostasis, platelets are also involved in the inflammatory and antimicrobial process. Interactions between pathogens and platelets,...
In addition to their role in haemostasis, platelets are also involved in the inflammatory and antimicrobial process. Interactions between pathogens and platelets, mediated by receptors can lead to platelet activation, which may be responsible for a granular secretion process or even aggregation, depending on the bacterial species. Granular secretion releases peptides with bactericidal activity as well as aggregating factors. To our knowledge, these interactions have been poorly studied for (). Few studies have characterised the cellular organization of platelet- aggregates. The objective of our study was to investigate the structure of platelet aggregates induced by different strains as well as the ultrastructure of platelet- mixtures using a scanning and transmission electron microscopy (SEM and TEM) approach. Our results show that the appearance of platelet aggregates is mainly dependent on the strain used. SEM images illustrate the platelet activation and aggregation and their colocalisation with bacteria. Some strains induce platelet activation and aggregation, and the bacteria are trapped in the platelet magma. However, some strains do not induce significant platelet activation and are found in close proximity to the platelets. The structure of the strains might explain the results obtained.
Topics: Humans; Escherichia coli; Blood Platelets; Escherichia coli Infections; Platelet Activation
PubMed: 36359892
DOI: 10.3390/cells11213495 -
American Journal of Physiology. Cell... Apr 2016Molecular chaperones that support protein quality control, including heat shock protein 70 (Hsp70), participate in diverse aspects of cellular and physiological...
Molecular chaperones that support protein quality control, including heat shock protein 70 (Hsp70), participate in diverse aspects of cellular and physiological function. Recent studies have reported roles for specific chaperone activities in blood platelets in maintaining hemostasis; however, the functions of Hsp70 in platelet physiology remain uninvestigated. Here we characterize roles for Hsp70 activity in platelet activation and function. In vitro biochemical, microscopy, flow cytometry, and aggregometry assays of platelet function, as well as ex vivo analyses of platelet aggregate formation in whole blood under shear, were carried out under Hsp70-inhibited conditions. Inhibition of platelet Hsp70 blocked platelet aggregation and granule secretion in response to collagen-related peptide (CRP), which engages the immunoreceptor tyrosine-based activation motif-bearing collagen receptor glycoprotein VI (GPVI)-Fc receptor-γ chain complex. Hsp70 inhibition also reduced platelet integrin-αIIbβ3 activation downstream of GPVI, as Hsp70-inhibited platelets showed reduced PAC-1 and fibrinogen binding. Ex vivo, pharmacological inhibition of Hsp70 in human whole blood prevented the formation of platelet aggregates on collagen under shear. Biochemical studies supported a role for Hsp70 in maintaining the assembly of the linker for activation of T cells signalosome, which couples GPVI-initiated signaling to integrin activation, secretion, and platelet function. Together, our results suggest that Hsp70 regulates platelet activation and function by supporting linker for activation of T cells-associated signaling events downstream of platelet GPVI engagement, suggesting a role for Hsp70 in the intracellular organization of signaling systems that mediate platelet secretion, "inside-out" activation of platelet integrin-αIIbβ3, platelet-platelet aggregation, and, ultimately, hemostatic plug and thrombus formation.
Topics: Blood Platelets; Flow Cytometry; HSP70 Heat-Shock Proteins; Humans; Integrins; Platelet Activation; Platelet Aggregation; Signal Transduction
PubMed: 26764050
DOI: 10.1152/ajpcell.00362.2015 -
International Journal of Molecular... Jun 2018In oncotherapy, ruthenium (Ru) complexes are reflected as potential alternatives for platinum compounds and have been proved as encouraging anticancer drugs with high... (Review)
Review
In oncotherapy, ruthenium (Ru) complexes are reflected as potential alternatives for platinum compounds and have been proved as encouraging anticancer drugs with high efficacy and low side effects. Cardiovascular diseases (CVDs) are mutually considered as the number one killer globally, and thrombosis is liable for the majority of CVD-related deaths. Platelets, an anuclear and small circulating blood cell, play key roles in hemostasis by inhibiting unnecessary blood loss of vascular damage by making blood clot. Platelet activation also plays a role in cancer metastasis and progression. Nevertheless, abnormal activation of platelets results in thrombosis under pathological settings such as the rupture of atherosclerotic plaques. Thrombosis diminishes the blood supply to the heart and brain resulting in heart attacks and strokes, respectively. While currently used anti-platelet drugs such as aspirin and clopidogrel demonstrate efficacy in many patients, they exert undesirable side effects. Therefore, the development of effective therapeutic strategies for the prevention and treatment of thrombotic diseases is a demanding priority. Recently, precious metal drugs have conquered the subject of metal-based drugs, and several investigators have motivated their attention on the synthesis of various ruthenium (Ru) complexes due to their prospective therapeutic values. Similarly, our recent studies established that novel ruthenium-based compounds suppressed platelet aggregation via inhibiting several signaling cascades. Our study also described the structure antiplatelet-activity relationship (SAR) of three newly synthesized ruthenium-based compounds. This review summarizes the antiplatelet activity of newly synthesized ruthenium-based compounds with their potential molecular mechanisms.
Topics: Animals; Blood Platelets; Humans; Molecular Targeted Therapy; Organometallic Compounds; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; Ruthenium; Thrombosis
PubMed: 29925802
DOI: 10.3390/ijms19061818 -
Nitric Oxide : Biology and Chemistry Feb 2021Nitric oxide, NO, has been explored as a therapeutic agent to treat thrombosis. In particular, NO has potential in treating mechanical device-associated thrombosis due...
Nitric oxide, NO, has been explored as a therapeutic agent to treat thrombosis. In particular, NO has potential in treating mechanical device-associated thrombosis due to its ability to reduce platelet activation and due to the central role of platelet activation and adhesion in device thrombosis. Nitrite is a unique NO donor that reduces platelet activation in that it's activity requires the presence of red blood cells whereas NO activity of other NO donors is blunted by red blood cells. Interestingly, we have previously shown that red blood cell mediated inhibition of platelet activation by adenosine diphosophate (ADP) is dramatically enhanced by illumination with far-red light that is likely due to photolysis of red cell surface bound NO congeners. We now report the effects of nitrite, far-red light, and their combination on several measure of blood coagulation using a variety of agonists. We employed turbidity assays in platelet rich plasma, platelet activation using flow cytometry analysis of a fluorescently labeled antibody to the activated platelet fibrinogen binding site, multiplate impedance-based platelet aggregometry, and assessment of platelet adhesion to collagen coated flow-through microslides. In all cases, the combination of far-red light and nitrite treatment decreased measures of coagulation, but in some cases mono-treatment with nitrite or light alone had no effect. Perhaps most relevant to device thrombosis, we observed that platelet adhesions was inhibited by the combination of nitrite and light treatment while nitrite alone and far-red light alone trended to decrease adhesion, but the results were mixed. These results support the potential of combined far-red light and nitrite treatment for preventing thrombosis in extra-corporeal or shallow-tissue depth devices where the far-red light can penetrate. Such a combined treatment could be advantageous due to the localized treatment afforded by far-red light illumination with minimal systemic effects. Given the role of thrombosis in COVID 19, application to treatment of patients infected with SARS Cov-2 might also be considered.
Topics: Blood Coagulation; Blood Platelets; COVID-19; Humans; Light; Nitric Oxide; Nitric Oxide Donors; Nitrites; Platelet Activation; Platelet Adhesiveness; Platelet Aggregation; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 33271226
DOI: 10.1016/j.niox.2020.11.005 -
TheScientificWorldJournal Feb 2002Adenosine diphosphate (ADP) plays a crucial role in hemostasis and thrombosis by activating platelets. In platelets, the classical P2T receptor is now resolved into... (Review)
Review
Adenosine diphosphate (ADP) plays a crucial role in hemostasis and thrombosis by activating platelets. In platelets, the classical P2T receptor is now resolved into three P2 receptor subtypes: the P2Y1, the P2Y12, and the P2X1 receptors. Both pharmacological and molecular biological approaches have confirmed the role of the P2Y1 and P2Y12 receptors in the ADP-induced platelet fibrinogen receptor activation. The P2Y1 and the P2X1 receptors independently contribute to platelet shape change. Whereas the P2Y12 receptor mediates the potentiation of dense granule release reaction, both the P2Y1 and P2Y12 receptors play an important role in the ADP-induced phospholipase A2 activation. The signaling events downstream of these receptors leading to the physiological effects remain elusive, and they are yet to be delineated.
Topics: Adenosine Diphosphate; Animals; Blood Platelets; Hemostasis; Humans; Phospholipases A; Phospholipases A2; Platelet Activation; Platelet Aggregation; Receptors, Purinergic P2; Thrombosis
PubMed: 12806027
DOI: 10.1100/tsw.2002.106 -
Journal of Thrombosis and Thrombolysis Jan 2014Platelets, anucleated cells with a central role in hemostasis and inflammation, contain messenger RNAs and microRNAs of unknown functionality and clinical relevance.... (Review)
Review
Platelets, anucleated cells with a central role in hemostasis and inflammation, contain messenger RNAs and microRNAs of unknown functionality and clinical relevance. Historically, platelet RNA was viewed as merely a remnant of platelet biogenesis; however, several studies now refute this assumption. Studies have shown that platelets can actively translate RNA to protein and that specific RNA profiles correlate with select human clinical phenotypes. These studies support a more fluid role for platelet RNA in platelet function and disease development. Our lab and others have recently studied the platelet's unique ability to transfer RNA to recipient cells and the effect this transfer has on the recipient cells' functions. This transfer may represent a previously unknown form of vascular cell communication and modulation. Unlike the well-characterized thrombotic properties of platelets, the nature and purpose of platelet RNA transfer has not been determined, partly due to limitations in techniques used to manipulate platelet RNA profiles. Defining the mechanism of RNA transfer and its role in the vascular system will allow for the better understanding of how platelets function in both their traditional thrombotic role and non-traditional functions, potentially having widespread implications in several fields.
Topics: Animals; Biomarkers; Blood Platelets; Humans; MicroRNAs; Platelet Activation; RNA, Messenger; Thrombosis
PubMed: 24163053
DOI: 10.1007/s11239-013-1001-1 -
International Journal of Molecular... Dec 2018Stroke, an important neurological disease, is becoming an increasingly non-communicable ailment and is the second leading cause of death after coronary heart disease in...
Stroke, an important neurological disease, is becoming an increasingly non-communicable ailment and is the second leading cause of death after coronary heart disease in developed countries [...].
Topics: Blood Platelets; Humans; Platelet Activation; Stroke
PubMed: 30567346
DOI: 10.3390/ijms19124103 -
Cold Spring Harbor Perspectives in... Feb 2012The adhesion and aggregation of platelets during hemostasis and thrombosis represents one of the best-understood examples of cell-matrix adhesion. Platelets are exposed... (Review)
Review
The adhesion and aggregation of platelets during hemostasis and thrombosis represents one of the best-understood examples of cell-matrix adhesion. Platelets are exposed to a wide variety of extracellular matrix (ECM) proteins once blood vessels are damaged and basement membranes and interstitial ECM are exposed. Platelet adhesion to these ECM proteins involves ECM receptors familiar in other contexts, such as integrins. The major platelet-specific integrin, αIIbβ3, is the best-understood ECM receptor and exhibits the most tightly regulated switch between inactive and active states. Once activated, αIIbβ3 binds many different ECM proteins, including fibrinogen, its major ligand. In addition to αIIbβ3, there are other integrins expressed at lower levels on platelets and responsible for adhesion to additional ECM proteins. There are also some important nonintegrin ECM receptors, GPIb-V-IX and GPVI, which are specific to platelets. These receptors play major roles in platelet adhesion and in the activation of the integrins and of other platelet responses, such as cytoskeletal organization and exocytosis of additional ECM ligands and autoactivators of the platelets.
Topics: Animals; Blood Platelets; Extracellular Matrix; Extracellular Matrix Proteins; Humans; Platelet Activation; Platelet Adhesiveness; Thrombosis
PubMed: 21937733
DOI: 10.1101/cshperspect.a005132 -
Anesthesiology Sep 1991Increases in plasma concentrations of platelet granule products such as platelet factor 4 and beta-thromboglobulin during cardiopulmonary bypass suggest that platelets...
Increases in plasma concentrations of platelet granule products such as platelet factor 4 and beta-thromboglobulin during cardiopulmonary bypass suggest that platelets are activated during extracorporeal circulation. Subsequent circulation of these activated platelets may be responsible for the ubiquitous platelet dysfunction associated with cardiopulmonary bypass. Using flow cytometry and a monoclonal antibody directed against an alpha-granule membrane protein, granule membrane protein 140 (GMP-140), which is expressed on the platelet surface membrane after activation, we directly measured the percentage of circulating activated platelets in 41 patients before, during, and after cardiopulmonary bypass. In addition, we compared the GMP-140 expression with platelet aggregation in response to adenosine diphosphate (ADP). Cardiopulmonary bypass produced a significant increase in the percentage of GMP-140-positive platelets persisting in the circulation; the percentage peaked at a mean of 29% (range 10-58%) before separation from extracorporeal circulation. A significant percentage of these activated platelets continued to circulate in the early postoperative period. Simultaneous measurement of platelet aggregation in response to ADP demonstrated an aggregation defect that had a time course distinct from platelet activation and whose magnitude did not correlate with the degree of platelet activation in individual patients. We conclude that cardiopulmonary bypass causes a complex constellation of platelet defects, which include alpha-granule release, prolonged circulation of activated, "spent" platelets, and impaired platelet aggregation.
Topics: Adenosine Diphosphate; Analysis of Variance; Antibodies, Monoclonal; Antigens, CD; Aortic Valve; Cardiopulmonary Bypass; Chest Tubes; Coronary Artery Bypass; Flow Cytometry; Heart Valve Prosthesis; Humans; P-Selectin; Platelet Activation; Platelet Aggregation; Platelet Membrane Glycoproteins; Time Factors
PubMed: 1716077
DOI: 10.1097/00000542-199109000-00002 -
Cell Transplantation 2016Delayed platelet engraftment is a well-known complication of umbilical cord blood transplantation (CBT). Megakaryocytes derived from cord blood (CB) in vitro are smaller... (Clinical Trial)
Clinical Trial
Delayed platelet engraftment is a well-known complication of umbilical cord blood transplantation (CBT). Megakaryocytes derived from cord blood (CB) in vitro are smaller than megakaryocytes derived from bone marrow (BM) in adults. A small megakaryocyte size might contribute to delayed megakaryocytic maturation. This study included 37 patients undergoing hematopoietic stem cell transplantation (HSCT) at Chang Gung Children's Hospital between July 2011 and June 2013. Blood samples were obtained at different times: preconditioning and post-HSCT days 56 and 97. To test whether platelet activation persists posttransplantation, two commonly used platelet activation marker antibodies, CD62P (P-selectin) and CD42b, were evaluated using whole blood flow cytometry, combining thiazole orange and anti-CD41a staining, to assess reticulated platelets. Serial peripheral blood (PB) samples were obtained posttransplantation from patients undergoing CBT (CBT group; n = 15) and mobilized peripheral blood transplantation (PBT group; n = 22). Platelet activation in the postengraftment samples was considerably higher in the PBT group than the CBT group. Moreover, immature platelet fractions (IPF) were higher in the CBT group. Our results emphasize the role of IPF for dynamic prediction of platelet engraftment in CBT.
Topics: Adolescent; Blood Platelets; Child; Child, Preschool; Demography; Female; Hematopoietic Stem Cell Transplantation; Humans; Infant; Male; Platelet Activation; Platelet Transfusion
PubMed: 26765743
DOI: 10.3727/096368916X690412