<br>血红素结合蛋白在血液相关疾病中的双刃作用：从基本机制到临床应用,Frontiers in Immunology

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血红素结合蛋白在血液相关疾病中的双刃作用：从基本机制到临床应用
Frontiers in Immunology ( IF 5.7 ) Pub Date : 2023-11-03 , DOI: 10.3389/fimmu.2023.1274333
Yijin Li ₁ , Renyu Chen ₁ , Chaofan Wang ₁ , Jun Deng ₁ , Shanshan Luo ₁

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现在人们了解到，溶血和随后释放到循环中的血红素在推动各种疾病的进展中发挥着关键作用。血红素结合蛋白 (HPX) 是一种对血浆中血红素具有最高亲和力的血红素结合蛋白，可有效拮抗严重急性或慢性溶血引起的血红素毒性。在本研究中，HPX浓度的变化在溶血性疾病的不同阶段进行了表征，强调了其作为评估疾病进展和预后的生物标志物的潜力。在许多血红素过载驱动的疾病中，例如镰状细胞病、输血引起的溶血和败血症，内源性 HPX 水平通常不足以提供保护。因此，人们对开发 HPX 疗法以减轻有毒血红素暴露越来越感兴趣。策略包括在内源性水平耗尽时补充 HPX，并通过修饰增强 HPX 的功能，从而有效防御血红素毒性。值得注意的是，HPX 在某些情况下也可能产生有害影响。本综述旨在全面概述 HPX 在血液疾病进展和预后中的作用。重点介绍了基于HPX的不同血液疾病的临床治疗方法，讨论了HPX生产和修饰技术的进展，为HPX的临床应用提供了理论基础。

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Double-edged functions of hemopexin in hematological related diseases: from basic mechanisms to clinical application

It is now understood that hemolysis and the subsequent release of heme into circulation play a critical role in driving the progression of various diseases. Hemopexin (HPX), a heme-binding protein with the highest affinity for heme in plasma, serves as an effective antagonist against heme toxicity resulting from severe acute or chronic hemolysis. In the present study, changes in HPX concentration were characterized at different stages of hemolytic diseases, underscoring its potential as a biomarker for assessing disease progression and prognosis. In many heme overload-driven conditions, such as sickle cell disease, transfusion-induced hemolysis, and sepsis, endogenous HPX levels are often insufficient to provide protection. Consequently, there is growing interest in developing HPX therapeutics to mitigate toxic heme exposure. Strategies include HPX supplementation when endogenous levels are depleted and enhancing HPX’s functionality through modifications, offering a potent defense against heme toxicity. It is worth noting that HPX may also exert deleterious effects under certain circumstances. This review aims to provide a comprehensive overview of HPX’s roles in the progression and prognosis of hematological diseases. It highlights HPX-based clinical therapies for different hematological disorders, discusses advancements in HPX production and modification technologies, and offers a theoretical basis for the clinical application of HPX.

更新日期：2023-11-03

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