Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA; Center for Blood Oxygen Transport and Hemostasis, Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD, USA.
Division of Internal Medicine, University Hospital, Zurich, Switzerland.
Trends Mol Med. 2020 Jul;26(7):683-697. doi: 10.1016/j.molmed.2020.02.004. Epub 2020 Mar 21.
Hemolysis and accumulation of cell-free hemoglobin (Hb) in the circulation or in confined tissue compartments such as the subarachnoid space is an important driver of disease. Haptoglobin is the Hb binding and clearance protein in human plasma and an efficient antagonist of Hb toxicity resulting from physiological red blood cell turnover. However, endogenous concentrations of haptoglobin are insufficient to provide protection against Hb-driven disease processes in conditions such as sickle cell anemia, sepsis, transfusion reactions, medical-device associated hemolysis, or after a subarachnoid hemorrhage. As a result, there is increasing interest in developing haptoglobin therapeutics to target 'toxic' cell-free Hb exposures. Here, we discuss key concepts of Hb toxicity and provide a perspective on the use of haptoglobin as a therapeutic protein.
溶血和游离血红蛋白 (Hb) 在循环或局限于组织间隙（如蛛网膜下腔）中的积累是疾病的重要驱动因素。触珠蛋白是人类血浆中与 Hb 结合和清除的蛋白，也是由于生理红细胞更新导致的 Hb 毒性的有效拮抗剂。然而，触珠蛋白的内源性浓度不足以在镰状细胞贫血、脓毒症、输血反应、与医疗器械相关的溶血或蛛网膜下腔出血后等情况下提供针对 Hb 驱动的疾病过程的保护。因此，人们越来越有兴趣开发触珠蛋白治疗药物来针对“毒性”游离 Hb 暴露。在这里，我们讨论了 Hb 毒性的关键概念，并提供了触珠蛋白作为治疗蛋白的应用视角。
