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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
Although the mechanism of action of intravenous immunoglobulin (IVIg) in treating antibody-dependent thrombocytopenia remains unclear, most studies have suggested that IVIg blocks the function of Fc receptors in the reticuloendothelial system (RES) and/or the protective effect may be due to the presence of variable region-reactive (anti-idiotype) antibodies within IVIg. We evaluated the effect of
Two flow cytometric parameters are generally used to quantify platelet activation as measured by P-selectin (CD62) expression: percentage and mean channel fluorescence of CD62-positive platelets (%+ and MCF+, respectively). We describe a method for calculation of indices of platelet activation for positive (IPA+) and total (IPA(Σ)) platelets, which reflect integrated amounts of CD62 expressed in t
Background and Objectives: Our objective was to study the effect of storage time on the filtration of platelet concentrates (PCs). We compared the total number of white blood cells (WBC), as well as the distribution of WBC subsets, in units filtered before and after storage. Materials and Methods: Buffy coat-derived PCs were filtered either fresh or after 5 days of storage, and total WBC were enum
Recipient IgG immunity against leukoreduced donor platelets is dependent on indirect T-cell allorecognition and is suppressed in vivo by inhibitors (aminoguanidine, AMG) of inducible nitric oxide synthase (INOS). To examine recipient processing pathways of donor platelet antigens, enriched macrophages (antigenpresenting cells [APC]) from BALB/c (H-2(d)) mice were pulsed with allogeneic C57BL/6 (H-
Platelet activation status (PAS) is used for characterizing quality and function of platelets in various experimental and clinical settings. In this study, we created a set of platelet populations differing in PAS, using stimulation of platelets with thrombin in a wide range of concentrations, and analyzed a number of flow cytometric parameters, which characterize PAS by measuring P-selectin (CD62
In a murine model of platelet alloimmunization, we examined the definitive role that mononuclear cells (MC) have in modulating platelet immunity by using platelets from severe combined immunodeficient (SCID) mice. CB.17 (H-2(d)) SCID or BALB/c (H-2(d)) mouse platelets were transfused weekly into fully allogeneic CBA (H-2(k)) mice and antidonor antibodies measured by flow cytometry. MC levels in BA
