Rationale: Effective and rapid bacterial clearance is a fundamental determinant of outcomes in sepsis. DJ-1 is a well-established reactive oxygen species (ROS) scavenger. Objectives: Because cellular ROS status is pivotal to inflammation and bacterial killing, we determined the role ofDJ-1 in bacterial sepsis. Methods: We used cell and murine models with gain- A nd loss-offunction experiments, pla

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusionrelated fatalities and is characterized by the onset of acute respiratory distress within six hours following blood transfusion. In most cases, donor antibodies are suggested to be involved, however, the pathogenesis is poorly understood. A two-hit model is generally assumed to underlie TRALI pathogenesis where the fi

Several biological medicines derived from human and animal plasmas can effectively improve haemostasis in individuals with inherited or acquired defects in haemostasis. Factor VIII and factor VIII/vWF and factor IX concentrates are used to treat haemophilia A, von Willebrand disease and hemophilia B respectively. Cryoprecipitates are used to treat hypofibrinogenemia and von Willebrand disease wher

BACKGROUND: Anti-D treatment is effective in increasing platelet (PLT) counts in patients with autoimmune thrombocytopenic purpura (AITP); however, the exact mechanism of action is unknown. Previous results have suggested that anti-D-coated red blood cells (RBCs) affect reticuloendothelial system phagocytosis by stimulating agents (e.g., reactive oxygen species) that alter signaling pathways withi

Platelets express Toll-like receptor 4 (TLR4), and this has been shown to be responsible for the thrombocytopenia induced by lipopolysaccharide (LPS) administration in vivo. We studied the role of LPS in mediating platelet phagocytosis by THP-1 cells in vitro by flow cytometry. Opsonization of platelets with an IgG monoclonal (W6/32) antibody or with IgG autoantibody-positive sera from patients wi

The exact mechanism of action of IVIg in the amelioration of immune thrombocytopenic purpura (ITP) is still unclear. Studies have suggested that IVIg may function through the regulation of cytokines, including interleukin-1 receptor antagonist (IL-1Ra), an inhibitor of phagocytosis. Using a mouse model relevant to ITP, we confirm an increase in mouse serum levels of IL-1Ra after exposure to IVIg,

Fetal and neonatal alloimmune thrombocytopenia (FNAITP) is a life-threatening bleeding disorder caused by maternal antibodies directed against fetal platelet antigens. The immunoreactive epitopes in FNAITP are primarily located in the extracellular regions of the platelet glycoprotein IIIa (β3 integrin). Here we have established a novel animal model of FNAITP using β3 integrin-deficient (β3-/-) mi

Toll-like receptors (TLRs) play a critical role in stimulating innate immunity by recognizing pathogen-associated molecular patterns (PAMPs) on invading microorganisms. Platelets also play a role in innate immunity, and we studied whether they express TLR. Results show that human and murine platelets variably expressed TLR2, TLR4, and TLR9 by flow cytometry and Western blotting. TLR4 expression wa

Autoimmune hemolytic anemia (AIHA) is an autoimmune disorder in which autoantibodies are directed against an individual's own red blood cells (RBCs), leading to enhanced clearance through Fc receptor (FcR)-mediated phagocytosis. Although there is a large literature relating to clinical aspects of AIHA, relatively little work addresses how IgG autoantibodies are actually produced against RBC autoan

BACKGROUND: Immunoglobulin G (IgG) anti-platelet (PLT) immunity has been shown to be initiated by indirect allorecognition where recipient T cells recognize donor PLT antigens presented by class II molecules encoded by the major histocompatibility complex (MHC) on recipient antigen-presenting cells. To understand how the recipient's MHC class II molecules may influence PLT alloimmunity, immune res

The mechanisms responsible for immunoglobulin G (IgG) immunity against allogeneic platelets are poorly understood. We studied the role that murine recipient CD8+ T and natural killer (NK) cells play in immunity against allogeneic platelets. BALB/c mice were depleted of the cells by cell-specific antibodies, transfused weekly with platelets from C57BL/6 mice, and serum IgG antidonor antibodies were

BACKGROUND: Development and characterization of methods for preventing transfusion-associated GVHD have utilized in vitro studies with human WBCs and in vivo studies in animal models. The limitation of these assays is that the in vivo GVHD response of treated human WBCs has not been tested directly. STUDY DESIGN AND METHODS: PBMNCs isolated from nonleukoreduced RBC units exposed to gamma irradiati

Previous results have demonstrated that anti-D therapy in children with chronic autoimmune thrombocytopenic purpura (AITP) induced a significant increase in several pro- and anti-inflammatory plasma cytokines within 2 hours of administration. To investigate the biologic basis of these early in vivo responses, we developed a flow cytometric assay to measure Fc-dependent responses of human periphera

Autoimmune thrombocytopenic purpura (AITP) is a bleeding disorder in which autoantibodies are directed against an individual's own platelets, leading to enhanced clearance through Fc receptor (R)-mediated phagocytosis by macrophages residing in the reticuloendothelial system (RES), particularly in the spleen. The production of IgG autoantibodies is critically dependent on cellular immune mechanism

It has previously been shown that sera from multiparous women have increased levels of anti-idiotypic antibodies specific for anti-HLA molecules. γ-Globulins prepared from these sera may be superior to commercial preparations of intravenous γ-globulin (IVIg) for inhibiting HLA alloimmunization. To test this, F(ab′)2 fragments prepared from either commercial IVIg or from the sera of men or multipar

Clinical studies have convincingly demonstrated that WBC reduction of blood components can reduce the incidence of primary HLA antigen alloimmunization at least in patients with acute myeloid leukemia.1 However, despite receiving WBC‐reduced platelets, approximately 19 percent of acute myeloid leukemia patients still became alloimmunized.1 In addition, it is not known whether WBC reduction will pr

Intravenous anti-D is often used in the treatment of autoimmune thrombocytopenic purpura (AITP), but little is known about its mechanisms of action. To investigate anti-D's potential in vivo mechanism(s) of action, a small group (N = 7) of children with chronic AITP was studied. The children initially received either 25 or 50 μg/kg of WinRho-SD in a four-cycle cross-over trial, and peripheral bloo