[Effects of abnormal Hb on red cell membranes].
Unstable hemoglobin disorders are due to substitutions or deletions of amino acids which alter the normal tertiary structure of hemoglobin and/or decrease heme-binding to globin. These changes result in enhanced oxidation to methemoglobin, rapid conversion of methemoglobin to hemichrome and sometimes heme loss, which leads to denaturation and precipitation as Heinz bodies. This process is associated with marked oxidative membrane damage, such as crosslinking of membrane proteins, membrane lipid peroxidation, hemin-induced destabilization of cytoskeletal protein interactions, and increased permeability to potassium ions. The damaged erythrocytes are sequestered in the spleen, where Heinz bodies are "pitted" or the entire cell is phagocytized by macrophages. The precise mechanisms leading to hemolysis are not fully understood. However, one hypothesis involves hemichrome binding to the cytoplasmic domain of band 3, leading to clustering of band 3 in the membrane and immunologic recognition of the redistributed band 3 by autologous senescent antibodies. This theory is based on immunologic findings rather than deformability changes, and it is consistent with many features of unstable hemoglobins.
Ideguchi
H
H
Department of Clinical Chemistry and Laboratory Medicine, School of Medicine, Fukuoka University.
D001323:Autoantibodies; D004910:Erythrocyte Membrane / Q000378:metabolism / Q000473:pathology; D006453:Hemoglobinopathies / Q000097:blood / Q000209:etiology; D006455:Hemoglobins, Abnormal / Q000276:immunology / Q000378:metabolism; D006461:Hemolysis; D006801:Humans; D018384:Oxidative Stress; D011489:Protein Denaturation
D001323:Autoantibodies; D006455:Hemoglobins, Abnormal