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.