Pb-Induced Eryptosis May Provoke Thrombosis Prior to Hemolysis.
Pb-Induced Eryptosis May Provoke Thrombosis Prior to Hemolysis.
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DOI：
10.3390/ijms23137008
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发表时间：
2022-06-23
影响因子：
5.6
通讯作者：
Pi, Jingbo
中科院分区：
文献类型：
--
作者：
Jin, Qiushuo;Yao, Chunyang;Bian, Yiying;Pi, Jingbo
关键词：
铅（Pb）是一种常见的金属，可通过水或食物的污染对人体有毒，并可引起贫血和其他疾病。然而，在铅中毒引起溶血和贫血之前会发生什么尚不清楚。在这里，我们证明铅可以引起红细胞的促凝活性，导致溶血前血栓形成。在新鲜分离的人红细胞中，我们观察到铅在浓度和时间上都能导致溶血，但在铅暴露的红细胞（≤20 μM, 1 h）中没有发生溶血。Pb处理在孵育0.5 h后未引起红细胞形状变化，但在孵育1 h时观察到棘球细胞和棘球细胞形状变化，表明Pb可以增强红细胞形状变化的浓度和时间依赖性。Pb处理后，ROS非依赖性凋亡表现为活性氧（ROS）不增加，但[Ca2+]i和caspase 3活性增加。在小鼠血栓模型中，我们观察到铅处理（0或25 mg/kg）增加了血栓。简而言之，在溶血之前，我们证明Pb可以引起ros独立但[Ca2+]i依赖的红细胞淤积，这可能引发血栓形成。
Lead (Pb) is a common metal, which can be toxic to the human body via the pollution of water or food, and can cause anemia and other diseases. However, what happens before hemolysis and anemia caused by Pb poisoning is unclear. Here, we demonstrated Pb can cause procoagulant activity of erythroid cells leading to thrombosis before hemolysis. In freshly isolated human erythroid cells, we observed that Pb resulted in hemolysis in both concentration- and time-dependent manners, but that no lysis occurred in Pb-exposed erythroid cells (≤20 μM for 1 h). Pb treatment did not cause shape changes at up to 0.5 h incubation but at 1 h incubation echinocyte and echino-spherocyte shape changes were observed, indicating that Pb can exaggerate a concentration- and time-dependent trend of shape changes in erythroid cells. After Pb treatment, ROS-independent eryptosis was shown with no increase of reactive oxygen species (ROS), but with an increase of [Ca2+]i and caspase 3 activity. With a thrombosis mouse model, we observed increased thrombus by Pb treatment (0 or 25 mg/kg). In brief, prior to hemolysis, we demonstrated Pb can cause ROS-independent but [Ca2+]i-dependent eryptosis, which might provoke thrombosis.
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