Acetylcholinesterase and lymphocyte function-associated antigen 3 found on decay-accelerating factor-negative erythrocytes from some patients with paroxysmal nocturnal hemoglobinuria are lost during erythrocyte aging.
Erythrocytes from patients with paroxysmal nocturnal hemoglobinuria are deficient in decay-accelerating factor (DAF), a factor called C8-binding protein or homologous restriction factor, acetylcholinesterase (AchE), and lymphocyte function-associated antigen 3 (LFA-3). These proteins share a common feature that glycan-inositolphospholipid anchors the protein to the membrane, suggesting that an abnormality related to this glycolipid causes multiple protein deficiencies. The relationship between the DAF, AchE, and LFA-3 defects was studied by fluorescent flow cytometric analysis. In five patients, DAF-negative erythrocytes were also AchE-negative. In three patients, a fraction of DAF-negative erythrocytes expressed subnormal levels of AchE, indicating that AchE was synthesized in these DAF-negative cells. Erythrocytes from the patients having DAF-negative, AchE-positive cells were separated according to density and analyzed for expression of DAF and AchE. Both proteins decreased with increase of cell density, suggesting that DAF-negative, AchE-positive cells become AchE-negative during erythrocyte maturation by losing AchE. A low level of LFA-3 was found on DAF-negative erythrocytes from one patient and decreased with erythrocyte maturation. These results support an idea that complete deficiency of glycan-inositolphospholipid-anchored proteins on erythrocytes could result from abnormally early termination of surface recruitment of these proteins, and subsequent dilution through cell divisions and loss from the surface.
Ueda
E
E
Department of Clinical Research, Osaka University, Japan.
Kinoshita
T
T
Terasawa
T
T
Shichishima
T
T
Yawata
Y
Y
Inoue
K
K
Kitani
T
T
D000110:Acetylcholinesterase / Q000097:blood*; D000954:Antigens, Surface / Q000097:blood*; D018958:CD55 Antigens; D018968:CD58 Antigens; D002469:Cell Separation; D004905:Erythrocyte Aging; D004912:Erythrocytes / Q000378:metabolism*; D005434:Flow Cytometry; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood*; D006801:Humans; D008562:Membrane Glycoproteins / Q000097:blood*; D008565:Membrane Proteins / Q000172:deficiency*; D012156:Reticulocytes / Q000378:metabolism
D000954:Antigens, Surface; D018958:CD55 Antigens; D018968:CD58 Antigens; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D000110:Acetylcholinesterase