During red blood cell (RBC) lysis hemoglobin and heme leak out of the cells and cause damage to the endothelium and nearby tissue. Protective mechanisms exist; however, these systems are not sufficient in diseases with increased extravascular hemolysis e.g. hemolytic anemia. α₁-microglobulin (A1M) is a ubiquitous reductase and radical- and heme-binding protein with antioxidation properties. Although present in the circulation in micromolar concentrations, its function in blood is unclear. Here, we show that A1M provides RBC stability. A1M^−/− mice display abnormal RBC morphology, reminiscent of macrocytic anemia conditions, i.e. fewer, larger and more heterogeneous cells. Recombinant human A1M (rA1M) reduced in vitro hemolysis of murine RBC against spontaneous, osmotic and heme-induced stress. Moreover, A1M is taken up by human RBCs both in vitro and in vivo. Similarly, rA1M also protected human RBCs against in vitro spontaneous, osmotic, heme- and radical-induced hemolysis as shown by significantly reduced leakage of hemoglobin and LDH. Addition of rA1M resulted in decreased hemolysis compared to addition of the heme-binding protein hemopexin and the radical-scavenging and reducing agents ascorbic acid and Trolox (vitamin E). Furthermore, rA1M significantly reduced spontaneous and heme-induced fetal RBC cell death. Addition of A1M to human whole blood resulted in a significant reduction of hemolysis, whereas removal of A1M from whole blood resulted in increased hemolysis. We conclude that A1M has a protective function in reducing hemolysis which is neither specific to the origin of hemolytic insult, nor species specific.

在红细胞 (RBC) 溶解期间，血红蛋白和血红素从细胞中泄漏出来，并对内皮和附近组织造成损害。存在保护机制；然而，这些系统不足以治疗血管外溶血增加的疾病，例如溶血性贫血。α ₁ -微球蛋白 (A1M) 是一种普遍存在的还原酶以及具有抗氧化特性的自由基和血红素结合蛋白。虽然以微摩尔浓度存在于循环中，但其在血液中的功能尚不清楚。在这里，我们表明 A1M 提供 RBC 稳定性。A1M ^-/-小鼠表现出异常的红细胞形态，让人联想到大红细胞性贫血状况，即更少、更大和更异质的细胞。重组人 A1M (rA1M)在体外减少小鼠红细胞溶血对抗自发性、渗透性和血红素诱导的应激。此外，A1M在体外和体内都被人红细胞吸收。同样，rA1M在体外也保护人类红细胞免受自发性、渗透性、血红素和自由基诱导的溶血，如显着减少的血红蛋白和 LDH 渗漏所示。与添加血红素结合蛋白 hemopexin 和自由基清除剂和还原剂抗坏血酸和 Trolox（维生素 E）相比，添加 rA1M 导致溶血减少。此外，rA1M 显着减少自发和血红素诱导的胎儿红细胞死亡。向人全血中添加 A1M 导致溶血显着减少，而从全血中去除 A1M 导致溶血增加。我们得出结论，A1M 在减少溶血方面具有保护功能，这既不是溶血损伤起源的特异性，也不是物种特异性的。