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Clinical Immunology (Orlando, Fla.) Oct 2023Markers of extracellular mitochondria are present in giant cell arteritis (GCA) patients. However, their role in promoting inflammation and platelet activation is no...
Markers of extracellular mitochondria are present in giant cell arteritis (GCA) patients. However, their role in promoting inflammation and platelet activation is no known. To investigate this, isolated mitochondria were opsonized with plasma from GCA patients or healthy individuals and incubated with peripheral blood mononuclear cells (PBMCs) or platelets and assessed for inflammatory cytokine production and platelet activation. Plasma from GCA patients promoted increased mitochondrial-mediated cytokine production by PBMCs as compared to healthy controls (p < 0.05). Mitochondria opsonized with plasma factors from patients with GCA induced higher platelet activation as compared to mitochondria opsonized with plasma factors from healthy individuals (p = 0.0015). Platelet levels of P-selectin were associated with disease activity in GCA (r = 0.34, p = 0.01). GCA patients have impaired ability to regulate the clearance of extracellular mitochondria, possibly contributing to excessive inflammation and platelet activation. Targeting key drivers of mitochondrial extrusion and/or their clearance could lead to new therapeutic interventions in GCA.
Topics: Humans; Giant Cell Arteritis; Leukocytes, Mononuclear; Inflammation; Platelet Activation; Cytokines
PubMed: 37625669
DOI: 10.1016/j.clim.2023.109746 -
Progress in Molecular and Subcellular... 2022Leukocytes are immune cells derived from hematopoietic stem cells of the bone marrow which play essential roles in inflammatory and immune responses. In contrast to... (Review)
Review
Leukocytes are immune cells derived from hematopoietic stem cells of the bone marrow which play essential roles in inflammatory and immune responses. In contrast to anucleate platelets and erythrocytes, leukocytes are differentiated from other blood cells by the presence of a nucleus, and consist of monocytes, neutrophils, lymphocytes, basophils, and eosinophils. Factors released from platelets mediate immune responses in part by recruitment and regulation of leukocyte activity. Platelet dense granules contain the highly anionic polymer polyphosphate (polyP) with monomer chain lengths of approximately 60-100 phosphates long, which are released into the microenvironment upon platelet activation. Recent studies suggest that polyP released from platelets plays roles in leukocyte migration, recruitment, accumulation, differentiation, and activation. Furthermore, bacterial-derived polyphosphate, generally consisting of phosphate monomer lengths in the hundreds to thousands, appear to play a role in pathogenic evasion of the host immune response. This review will discuss the effects of host and pathogenic-derived polyphosphate on leukocyte function.
Topics: Blood Platelets; Leukocyte Count; Leukocytes; Platelet Activation; Polyphosphates
PubMed: 35697939
DOI: 10.1007/978-3-031-01237-2_6 -
Frontiers in Immunology 2021In 2019 10 million people developed symptomatic tuberculosis (TB) disease and 1.2 million died. In active TB the inflammatory response causes tissue destruction, which... (Review)
Review
In 2019 10 million people developed symptomatic tuberculosis (TB) disease and 1.2 million died. In active TB the inflammatory response causes tissue destruction, which leads to both acute morbidity and mortality. Tissue destruction in TB is driven by host innate immunity and mediated enzymes, chiefly matrix metalloproteinases (MMPs) which are secreted by leukocytes and stromal cells and degrade the extracellular matrix. Here we review the growing evidence implicating platelets in TB immunopathology. TB patients typically have high platelet counts, which correlate with disease severity, and a hypercoagulable profile. Platelets are present in human TB granulomas and platelet-associated gene transcripts are increased in TB patients versus healthy controls. Platelets most likely drive TB immunopathology through their effect on other immune cells, particularly monocytes, to lead to upregulation of activation markers, increased MMP secretion, and enhanced phagocytosis. Finally, we consider current evidence supporting use of targeted anti-platelet agents in the treatment of TB due to growing interest in developing host-directed therapies to limit tissue damage and improve treatment outcomes. In summary, platelets are implicated in TB disease and contribute to MMP-mediated tissue damage their cellular interactions with other leukocytes, and are potential targets for novel host-directed therapies.
Topics: Blood Platelets; Extracellular Matrix; Humans; Immunity, Innate; Inflammation; Leukocytes; Platelet Activation; Platelet Aggregation Inhibitors; Signal Transduction; Tuberculosis
PubMed: 34093524
DOI: 10.3389/fimmu.2021.631696 -
Platelets Feb 2022While it is clear that platelets interact with viruses, the ramifications and mechanisms of those interactions are still being defined for each type of viral infection....
While it is clear that platelets interact with viruses, the ramifications and mechanisms of those interactions are still being defined for each type of viral infection. HIV/AIDS represents a potentially unique example of how viremia affects platelets since the increasing efficacy of antiretroviral therapeutics (ART) has made it a chronic disease that increases the risk of cardiovascular disease. In this opinion article, we discuss some of the open questions about how platelets interact with HIV. What happens to a virion once it binds a platelet? What is the nature of virus-induced platelet activation? Are platelets a normal part of the immune response to viremia that has been co-opted to increase the spread of HIV? The answers to these and similar questions will help define how platelet-directed therapeutics might be used in treating HIV/AIDS patients.
Topics: Blood Platelets; HIV Infections; Humans; Platelet Activation
PubMed: 35086429
DOI: 10.1080/09537104.2021.2019695 -
Circulation Research Apr 2023
Topics: Humans; Platelet Activation; Thrombosis; Blood Platelets; Inflammation
PubMed: 37104561
DOI: 10.1161/CIRCRESAHA.123.322780 -
Platelets May 2020Platelets are small, anucleated effector cells that play an important role in linking the hemostatic and inflammatory processes in the body. Platelet function is known... (Review)
Review
Platelets are small, anucleated effector cells that play an important role in linking the hemostatic and inflammatory processes in the body. Platelet function is known to be altered under various inflammatory conditions including aging. A gain in platelet function during aging can increase the risk of thrombotic events, such as stroke and acute myocardial infarction. Anti-platelet therapy is designed to reduce risk of serious cerebrovascular and cardiovascular events, but the adverse consequences of therapy, such as risk for bleeding increases with aging as well. Age-associated comorbidities such as obesity, diabetes, and hyperlipidemia also contribute to increased platelet activity and thus can enhance the risk of thrombosis. Therefore, identification of unique mechanisms of platelet dysfunction in aging and in age-associated comorbidities is warranted to design novel antiplatelet drugs. This review outlines some of the current areas of research on aging-related mechanisms of platelet hyperactivity and addresses the clinical urgency for designing anti-platelet therapies toward novel molecular targets in the aging population.
Topics: Aged; Aging; Animals; Blood Platelet Disorders; Blood Platelets; Comorbidity; Humans; Inflammation; Oxidative Stress; Platelet Activation; Risk Factors; Signal Transduction; Thrombosis
PubMed: 31524038
DOI: 10.1080/09537104.2019.1665641 -
Platelets May 2022Platelets are essential mediators of physiological hemostasis and pathological thrombosis. Currently available tests and markers of platelet activation did not prove... (Review)
Review
Platelets are essential mediators of physiological hemostasis and pathological thrombosis. Currently available tests and markers of platelet activation did not prove successful in guiding treatment decisions for patients with cardiovascular disease, justifying further research into novel markers of platelet reactivity. Platelets contain a variety of microRNAs (miRNAs) and are a major contributor to the extracellular circulating miRNA pool. Levels of platelet-derived miRNAs in the circulation have been associated with different measures of platelet activation as well as antiplatelet therapy and have therefore been implied as potential new markers of platelet reactivity. In contrast to the assessment of platelet reactivity by current platelet function tests, miRNA measurements may enable assessment of platelet reactivity . It remains to be seen however, whether miRNAs may aid clinical diagnostics. Major limitations in the platelet miRNA research field remain the susceptibility to preanalytical variation, non-standardized sample preparation and data normalization that hampers inter-study comparisons. In this review, we provide an overview of the literature on circulating miRNAs as biomarkers of platelet activation, highlighting the underlying biology, the application in patients with cardiovascular disease and antiplatelet therapy and elaborating on technical limitations regarding their quantification in the circulation.
Topics: Biomarkers; Blood Platelets; Cardiovascular Diseases; Circulating MicroRNA; Humans; MicroRNAs; Platelet Activation; Platelet Aggregation Inhibitors
PubMed: 35264060
DOI: 10.1080/09537104.2022.2042236 -
Circulation Research Mar 2023Platelets are small, anucleate entities that bud from megakaryocytes in the bone marrow. Among circulating cells, platelets are the most abundant cell, traditionally... (Review)
Review
Platelets are small, anucleate entities that bud from megakaryocytes in the bone marrow. Among circulating cells, platelets are the most abundant cell, traditionally involved in regulating the balance between thrombosis (the terminal event of platelet activation) and hemostasis (a protective response to tissue injury). Although platelets lack the precise cellular control offered by nucleate cells, they are in fact very dynamic cells, enriched in preformed RNA that allows them the capability of de novo protein synthesis which alters the platelet phenotype and responses in physiological and pathological events. Antiplatelet medications have significantly reduced the morbidity and mortality for patients afflicted with thrombotic diseases, including stroke and myocardial infarction. However, it has become apparent in the last few years that platelets play a critical role beyond thrombosis and hemostasis. For example, platelet-derived proteins by constitutive and regulated exocytosis can be found in the plasma and may educate distant tissue including blood vessels. First, platelets are enriched in inflammatory and anti-inflammatory molecules that may regulate vascular remodeling. Second, platelet-derived microparticles released into the circulation can be acquired by vascular endothelial cells through the process of endocytosis. Third, platelets are highly enriched in mitochondria that may contribute to the local reactive oxygen species pool and remodel phospholipids in the plasma membrane of blood vessels. Lastly, platelets are enriched in proteins and phosphoproteins which can be secreted independent of stimulation by surface receptor agonists in conditions of disturbed blood flow. This so-called biomechanical platelet activation occurs in regions of pathologically narrowed (atherosclerotic) or dilated (aneurysmal) vessels. Emerging evidence suggests platelets may regulate the process of angiogenesis and blood flow to tumors as well as education of distant organs for the purposes of allograft health following transplantation. This review will illustrate the potential of platelets to remodel blood vessels in various diseases with a focus on the aforementioned mechanisms.
Topics: Humans; Blood Platelets; Cell-Derived Microparticles; Endothelial Cells; Hemostasis; Platelet Activation; Thrombosis
PubMed: 36927182
DOI: 10.1161/CIRCRESAHA.122.321566 -
Hamostaseologie Apr 2023
Topics: Humans; Blood Platelets; Monocytes; Platelet Activation; Purinergic P2Y Receptor Antagonists
PubMed: 37100063
DOI: 10.1055/s-0043-1768490 -
Microbiology Spectrum Dec 2022Streptococcus bovisStreptococcus equinus complex (SBSEC) is a common cause of infective endocarditis (IE). For IE-pathogens, the capacity to activate and aggregate...
Streptococcus bovisStreptococcus equinus complex (SBSEC) is a common cause of infective endocarditis (IE). For IE-pathogens, the capacity to activate and aggregate platelets is believed to be an important virulence mechanism. While the interactions between bacteria and platelets have been described in detail for many Gram-positive pathogens, little research has been carried out with SBSEC in this respect. Twenty-six isolates of the four most common species and subspecies of SBSEC identified in bacteremia were collected, and interactions with platelets were investigated in platelet rich plasma (PRP) from three donors. Aggregation was studied using light-transmission aggregometry and platelet activation using flow cytometry detecting surface upregulation of CD62P. Platelets and serum were treated with different inhibitors to determine mechanisms involved in platelet aggregation and activation. Twenty-two of 26 isolates induced aggregation in at least one donor, and four isolates induced aggregation in all three donors. In PRP from donor 1, isolate SL1 induced a rapid aggregation with a median time of 70 s to reach 50% aggregation. Blockade of the platelet Fc-receptor or enzymatic cleavage of IgG abolished platelet activation and aggregation. The capacity for bacteria-induced platelet aggregation was also shown to be transferable between donors through serum. SBSEC mediates platelet aggregation in an IgG and IgG-Fc-receptor dependent manner. Bacterial activation of platelets through this pathway is common for many bacteria causing IE and could be a potential therapeutic target for the prevention and treatment of this infection. The capacity of bacteria to activate and aggregate platelets is believed to contribute to the pathogenesis of IE. The Streptococcus bovis/Streptococcus equinus complex (SBSEC) contains known IE-pathogens, but there is limited research on the different subspecies ability to interact with platelets and what signaling pathways are involved. This study reports that 22 of 26 tested isolates of different subspecies within SBSEC can induce aggregation, and that aggregation is host dependent. The Fc-IgG-receptor pathway was shown essential for platelet activation and aggregation. To the best of our knowledge, this is the first study that reports on platelet interactions of SBSEC-isolates other than Streptococcus gallolyticus subspecies as well as the first study to report of mechanisms of platelet interaction of SBSEC-isolates. It adds SBSEC to a group of bacteria that activate and aggregate platelets via the platelet Fc-receptor. This could be a potential therapeutic target for prevention of IE.
Topics: Streptococcus bovis; Platelet Activation; Platelet Aggregation; Blood Platelets; Immunoglobulin G
PubMed: 36374116
DOI: 10.1128/spectrum.01861-22