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Nouvelle cuisine : platelets served with inflammation
Platelets are small cellular fragments with the primary physiological role of maintaining hemostasis. In addition to this well-described classical function, it is becoming increasingly clear that platelets have an intimate connection with infection and inflammation. This stems from several platelet characteristics, including their ability to bind infectious agents and secrete many immunomodulatory
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C-reactive protein boosts antibody-mediated platelet destruction
Platelets release mitochondria serving as substrate for bactericidal group IIA-secreted phospholipase A2 to promote inflammation
Mitochondrial DNA (mtDNA) is a highly potent inflammatory trigger and is reportedly found outside the cells in blood in various pathologies. Platelets are abundant in blood where they promote hemostasis. Although lacking a nucleus, platelets contain functional mitochondria. On activation, platelets produce extracellular vesicles known as microparticles. We hypothesized that activated platelets cou
A comprehensive study of ovine haemostasis to assess suitability to model human coagulation
INTRODUCTION: Similarities in size, anatomy and physiology have supported the use of sheep to model a wide range of human diseases, including coagulopathy. However, coagulation studies involving sheep are limited by the absence of high quality data defining normal ovine coagulation and fibrinolysis.MATERIALS AND METHODS: Full blood examination, routine and specialised coagulation tests, rotational
Platelet GPIb-IX has suppressive effects on septic inflammation
A comparative study of different burning time models for the combustion of aluminum dust particles
In the present paper combustion of micron-sized aluminum dust cloud has been studied in a quiescent reaction medium with spatially discrete sources. A new thermal model is generated to estimate the flame front speed in a lean reaction environment in different oxidizer concentrations. Different burning time models for aluminum are utilized in the generated thermal model to compare their applicabili
Peripheral blood monocyte-derived chemokine blockade prevents murine transfusion-related acute lung injury (TRALI)
Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality and can occur with any type of transfusion. TRALI is thought to be primarily mediated by donor antibodies activating recipient neutrophils resulting in pulmonary endothelial damage. Nonetheless, details regarding the interactions between donor antibodies and recipient factors are unknown. A murine a
Pathogenesis of immune thrombocytopenia
Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by antibody-mediated platelet destruction. The platelet, as an accessible target, has made ITP an attractive disorder in the study of autoimmunity. However, the pathogenesis of ITP has proven complex with diverse pre-existing challenges to the immune system in the form of infection, genetic predisposition, underlying autoimmune
Allogeneic platelet transfusions prevent murine T-cell-mediated immune thrombocytopenia
Platelet transfusions are life-saving treatments for many patients with thrombocytopenia; however, their use is generally discouraged in the autoimmune disorder known as immune thrombocytopenia (ITP). We examined whether allogeneic platelet major histocompatibility complex (MHC) class I transfusions affected antiplatelet CD61-induced ITP. BALB/c CD61 knockout mice (CD61(-)/H-2(d)) were immunized a
Cellular immune dysfunction in immune thrombocytopenia (ITP)
Over the past decades, a wealth of information has been reported about the pathogenic features of immune thrombocytopenia (ITP). To this day, however, it is unclear whether the immune abnormalities associated with ITP play causative roles in the disease or are secondary epiphenomena brought on by the inflammatory processes that are associated with the disorder. Like the majority of all autoimmune
Platelets deliver small packages of genetic function
In this issue of Blood, Laffont et al have identified a type of delivery system by platelets in the form of platelet microparticles delivering functional microRNA to endothelial cells. The delivery, it appears, may be a relatively novel process of regulation of gene expression in endothelial cells and potentially other nucleated cells of the body.
Innate and adaptive immunity in immune thrombocytopenia
Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by both accelerated clearance of autoantibody-sensitized platelets and suboptimal platelet production. A number of studies have provided evidence of disturbed innate and adaptive immune responses in patients with ITP. This brief review will highlight some of the more recent work in this field and highlight other findings that pr
Bregging rights in ITP
T granules in human platelets function in TLR9 organization and signaling
Human and murine platelets (PLTs) variably express toll-like receptors (TLRs), which link the innate and adaptive immune responses during infectious inflammation and atherosclerotic vascular disease. In this paper, we show that the TLR9 transcript is specifically up-regulated during pro-PLT production and is distributed to a novel electron-dense tubular system-related compartment we have named the
Thymic retention of CD4+CD25+FoxP3+ T regulatory cells is associated with their peripheral deficiency and thrombocytopenia in a murine model of immune thrombocytopenia
Immune thrombocytopenia (ITP) is a bleeding disorder in which antibodies and/or T cells lead to enhanced peripheral platelet destruction and reduced bone marrow platelet production. Several reports have observed that ITP is associated with a peripheral deficiency of tolerance-inducing CD4+CD25+FoxP3+ T regulatory cells (Tregs). Using a murine model of ITP, we analyzed Tregs in the spleen and thymu
The immunopathogenesis of immune thrombocytopenia : T cells still take center-stage
PURPOSE OF REVIEW: Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder in which T and B cells recognize platelet antigens and initiate antiplatelet destructive mechanisms such as peripheral Fc receptor-mediated phagocytosis in the spleen or megakaryocyte destruction/inhibition within the bone marrow. The purpose of this review is to report on the ITP pathophysiology literature publish
HLA alloimmunization against platelet transfusions : pathophysiology, significance, prevention and management
Approximately five decades ago, alloimmunization to human leukocyte antigens (HLA) and platelet refractoriness were recognized as potentially serious complications of platelet transfusions. The mechanisms that result in stimulating immunity against blood products are still incompletely understood but are related to both the composition of the donor product transfused and the immune status of the r
Intravenous immunoglobulin prevents murine antibody-mediated acute lung injury at the level of neutrophil reactive oxygen species (ROS) production
Transfusion-related acute lung injury (TRALI) is a leading cause of transfusion-associated mortality that can occur with any type of transfusion and is thought to be primarily due to donor antibodies activating pulmonary neutrophils in recipients. Recently, a large prospective case controlled clinical study of cardiac surgery patients demonstrated that despite implementation of male donors, a high
