Thrombopoietin receptor agonist (TPO-RA) treatment raises platelet counts and reduces anti-platelet antibody levels in mice with immune thrombocytopenia (ITP).
Kapur Rick,Aslam Rukhsana,Speck Edwin R,Rebetz Johan M,Semple John W
Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder in which autoantibodies and/or autoreactive T cells destroy platelets and megakaryocytes in the spleen and bone marrow, respectively. Thrombopoietin receptor agonists (TPO-RA e.g. Romiplostim and Eltrombopag) have made a substantial contribution to the treatment of patients with ITP, which are refractory to first-line treatments and approximately 30% demonstrate sustained elevated platelet counts after drug tapering. How TPO-RA induce these sustained responses is not known. We analyzed the efficacy of a murine TPO-RA in a well-established murine model of active ITP. Treatment with TPO-RA (10 ug/kg, based on pilot dose escalation experiments) significantly raised the platelet counts in ITP-mice. Immunomodulation was assessed by measuring serum IgG anti-platelet antibody levels; TPO-RA-treated mice had significantly reduced IgG anti-platelet antibodies despite the increasing platelet counts. These results suggest that TPO-RA is not only an efficacious therapy but also reduces anti-platelet humoral immunity in ITP.
The potential contribution and role of a blood platelets in autoimmune thyroid diseases.
Tomczyńska Małgorzata,Salata Ireneusz,Bijak Michał,Saluk-Bijak Joanna
Journal of cellular and molecular medicine
The blood platelets are multifunctional blood cells which are involved in the initiation of atheroma, endothelial dysfunction, and modulation of inflammatory and immune responses in the pathophysiology of many diseases. Because of their multifaceted pro-inflammatory activity, platelets may be involved in the pathogenesis of autoimmune thyroid diseases (AITDs), such as Hashimoto's thyroiditis and Graves' disease. The aim of this study was to assess the level of activation and response ability of platelets in AITDs. We used the flow cytometry technique and kinetic measurement of aggregation to analyse platelet function immediately after blood collection and to demonstrate their activation in the circulation of patients with AITDs. We noted reorganization of platelet subpopulations (normal platelets, microparticles and aggregates) in AITDs, dependent on the degree of cell activation. We proved the elevated expression of the active form of integrin receptor GPIIb/IIIa, responsible for platelet aggregation, and in the kinetic test we confirmed the increased aggregation of platelets in different intracellular signal pathways (dependent on ADP, collagen, arachidonic acid). Our study demonstrates the high platelet activation level found in AITDs.
Effects of functionalized silver nanoparticles on aggregation of human blood platelets.
Hajtuch Justyna,Hante Nadhim,Tomczyk Ewelina,Wojcik Michal,Radomski Marek Witold,Santos-Martinez Maria Jose,Inkielewicz-Stepniak Iwona
International journal of nanomedicine
Purpose:We studied the effects of silver nanoparticles (AgNPs) on human blood platelet function. We hypothesized that AgNPs, a known antimicrobial agent, can be used as blood-compatible, "ideal material'' in medical devices or as a drug delivery system. Therefore, the aim of the current study was to investigate if functionalized AgNPs affect platelet function and platelets as well as endothelial cell viability in vitro. Methods:AgNPs, functionalized with reduced glutathione (GSH), polyethylene glycol (PEG) and lipoic acid (LA) were synthesized. Quartz crystal microbalance with dissipation was used to measure the effect of AgNPs on platelet aggregation. Platelet aggregation was measured by changes in frequency and dissipation, and the presence of platelets on the sensor surface was confirmed and imaged by phase contrast microscopy. Flow cytometry was used to detect surface abundance of platelet receptors. Lactate dehydrogenase test was used to assess the potential cytotoxicity of AgNPs on human blood platelets, endothelial cells, and fibroblasts. Commercially available ELISA tests were used to measure the levels of thromboxane B and metalloproteinases (MMP-1, MMP-2) released by platelets as markers of platelet activation. Results:2 nm AgNPs-GSH, 3.7 nm AgNPs-PEG both at 50 and 100 µg/mL, and 2.5 nm AgNPs-LA at 100 µg/mL reduced platelet aggregation, inhibited collagen-mediated increase in total P-selectin and GPIIb/IIIa, TXB2 formation, MMP-1, and MMP-2 release. The tested AgNPs concentrations were not cytotoxic as they did not affect, platelet, endothelial cell, or fibroblast viability. Conclusion:All tested functionalized AgNPs inhibited platelet aggregation at nontoxic concentrations. Therefore, functionalized AgNPs can be used as an antiplatelet agent or in design and manufacturing of blood-facing medical devices, such as vascular grafts, stents, heart valves, and catheters.