溶血与血栓形成和血管功能障碍有关,这是许多疾病的病理成分。溶血产品,包括血红蛋白和血红素,激活血小板(PLT)。尽管它被激活了,溶血对血小板清除的影响尚不清楚,维持正常的血小板计数和确保循环血小板在功能上存活是至关重要的。在这项研究中,我们用了血红素,血红蛋白的降解产物,作为治疗血小板和模拟小鼠体内变化的有效激动剂。Hemin处理诱导血小板活化和形态变化,包括细胞内Ca2+水平的增加,磷脂酰丝氨酸(PS)暴露,和细胞骨架重排。输血后肝脏中的巨噬细胞清除的血红素处理的血小板少于未处理的血小板。Hemin与糖蛋白Ibα(GPIbα)结合,血红素诱导的血小板活化和聚集的表面受体。此外,血红素降低了GPIbα脱盐作用,蓖麻凝集素I(RCA-I)结合减少,这可能延长了这种血小板在体内的寿命。这些数据为GPIbα介导的血小板活化和清除在溶血性疾病中的机制提供了新的见解。
背景是什么?溶血是一种原发性血液病。溶血是几种疾病的病理并发症。Hemin,一种无细胞血红蛋白的降解产物,已被证明是比血红蛋白更有效的激动剂,可直接激活血小板。血小板膜糖蛋白(GP),包括GPIb-IX和GPIIb/IIIa复合物,在血小板止血中起着至关重要的作用。GPIbα的去唾液酸化(唾液酸残基的损失),被认为通过肝巨噬细胞和肝细胞调节生理性血小板清除。什么是新的?在这项研究中,我们评估了溶血对血小板清除的影响.我们首先分析了0-50μM的血红素对血小板的影响,然后探索了血红素诱导的血小板活化的机制及其在体外和体内清除血小板的作用。我们的分析表明:血红素以高亲和力与血小板表面的GPIbα结合。血红素治疗后,肝脏和脾脏的血小板清除缓慢。血红素处理后,血小板表现出显着降低的GPIbα表面表达和去唾液酸化。血红素处理后,血小板表现出显着降低的GPIbα表面表达和去唾液酸化。影响是什么?这项研究为血红素在与溶血相关的疾病中GPIbα介导的血小板活化和清除机制中的作用提供了新的见解。
Hemolysis is associated with thrombosis and vascular dysfunction, which are the pathological components of many diseases. Hemolytic products, including hemoglobin and hemin, activate platelets (PLT). Despite its activation, the effect of
hemolysis on platelet clearance remains unclear, It is critical to maintain a normal platelet count and ensure that circulating platelets are functionally viable. In this study, we used hemin, a degradation product of hemoglobin, as a potent agonist to treat platelets and simulate changes in vivo in mice. Hemin treatment induced activation and morphological changes in platelets, including an increase in intracellular Ca2+ levels, phosphatidylserine (PS) exposure, and cytoskeletal rearrangement. Fewer hemin-treated platelets were cleared by macrophages in the liver after transfusion than untreated platelets. Hemin bound to glycoprotein Ibα (GPIbα), the surface receptor in hemin-induced platelet activation and aggregation. Furthermore, hemin decreased GPIbα desialylation, as evidenced by reduced Ricinus communis agglutinin I (RCA- I) binding, which likely extended the lifetime of such platelets in vivo. These data provided new insight into the mechanisms of GPIbα-mediated platelet activation and clearance in hemolytic disease.
What is the context?
Hemolysis is a primary hematological disease.
Hemolysis is a pathological complication of several diseases.Hemin, a degradation product of cell-free hemoglobin, has been proven to be a more potent agonist than hemoglobin for directly activating platelets.Platelet membrane glycoproteins (GP), including GPIb-IX and GPIIb/IIIa complexes, play crucial roles in platelet hemostasis.Desialylation (loss of sialic acid residues) of GPIbα, is believed to regulate physiological platelet clearance through liver macrophages and hepatocytes.What is new? In this study, we evaluated the effects of
hemolysis on platelet clearance. We first analyzed the influence of hemin at 0-50 μM on platelets in vitro before exploring the mechanism underlying hemin-induced platelet activation and its role in platelet clearance in vitro and in vivo.Our analyses suggest that: Hemin bound to GPIbα on the platelet surface with high affinity.Platelet clearance occurred slowly in the liver and spleen after hemin treatment.Platelets exhibited significant significantly reduced GPIbα surface expression and desialylation after hemin treatment.Platelets exhibited significant significantly reduced GPIbα surface expression and desialylation after hemin treatment.What is the impact? This study provides new insights into the role of hemin in the mechanisms of GPIbα-mediated platelets activation and clearance in diseases associated with hemolysis.