Erythrocyte Membrane Abnormalities: Alterations in the Chemical Composition and Physicochemical Properties

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The relationship between morphology and lipid composition of red blood cells in patients with hepatobiliary disease has been clearly demonstrated by several investigators. Little information is, however, available regarding the mechanism by which erythrocyte membrane abnormalities are induced. In order to clarify such mechanism, biochemical, ultrastructural and physiochemical studies of red blood cell membranes from patients with biliary obstruction and congenital biliary atresia have been carried out. Scanning electron microscope observation revealed that red blood cells from patients with biliary atresia classified as Group I (red cell lecithin≥41%) are mostly of the "target" type. On the other hand, red blood cells from Group III (red cell lecithin<31%) are almost normal biconcave disks. Phospholipids and free cholesterol were increased strikingly in red blood cells from Group I, whereas no significant difference was observed between Group III and control. The abnormalities in the lipid profile as well as morphology are dependent upon the degree of biliary obstruction. It is obvious that increase in the phospholipid content is principally due to an increment of lecithin. The analysis of the fatty acid composition of lecithin revealed a similar pattern in red blood cell membranes, plasma and bile. It is of particular interest that the lecithin fatty acid composition of lipoprotein-X (LP-X) was found to be quite similar to that of erythrocyte membranes. On the other hand, in spite of little change in the lipid content of erythrocyte membranes, the lecithin fatty acid composition of erythrocyte membranes and plasma in Group III showed a similar but smaller change compared to that of patients in Group I. Freeze-fracture electron microscopy showed significant alterations in Group I membranes, such as depressions on the fracture faces and reduced density of membrane particles (3,584→2,432/μm2) on the protoplasmic face. Electron spin resonance studies on erythrocyte membranes labeled with 5-nitroxide stearate demonstrated that the erythrocyte membranes from Group I are more fluid than the control membranes. Consequently, two working hypotheses were proposed by which excess membrane may be incorporated into erythrocyte membranes; fusion of LP-X with erythrocyte membranes (Group I) and exchange of lipids between erythrocyte membranes and plasma lipoproteins (Group III). Red blood cells from patients with congenital biliary atresia exhibited a wide variation in the morphology, such as target, spur and cup formed cells. By freeze-fracture electron microscopy, membrane particle-free areas were prominent in the fracture faces and the density of membrane particles were 20% lower than those of control subjects. Both free cholesterol and phospholipids were found to be increased in erythrocyte membranes from patients with congenital biliary atresia. In addition, the fatty acid composition of erythrocyte lecithin was similar to that of acquired biliary obstruction. Fluorescence polarization studies by using fluorescent probe, 1, 6-diphenyl-1, 3, 5-hexatriene (DPH) on red blood cells demonstrated that erythrocyte membrane lipids from patient are less fluid than those of control subject. From the similarity of lipid alterations to those observed with acquired biliary obstruction and the fact that LP-X was found in all patients examined, it is reasonable to consider that LP-X might be involved in causing erythrocyte membrane abnormalities in congenital biliary atresia.
Japan Society of Clinical Chemistryの論文

Erythrocyte Membrane Abnormalities: Alterations in the Chemical Composition and Physicochemical Properties

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