Decreased erythrocyte membrane fluidity and altered lipid composition in human liver disease

Abstract

Abnormal plasma lipoproteins in patients with liver disease are associated with characteristic changes in erythrocyte membrane lipid composition. The membranes are enriched in cholesterol and phosphatidylcholine and both the cholesterol/phospholipid and phosphatidylcholine/sphingomyelin molar ratios are increased. Phospholipid fatty acid composition is also abnormal; the proportions of arachidonic acid and stearic acid are decreased and that of palmitic acid raised. In this study we have examined the effects of these membrane lipid abnormalities on membrane fluidity. Erythrocyte membrane fluidity was assessed in 30 patients with a variety of liver diseases and in 25 normal subjects using the hydrophobic, fluorescent probe 1,6-diphenylhexa-1,3,5-triene and the values were related to their lipid composition. Membrane fluidity was significantly decreased in the patient erythrocytes (lipid order parameter, S(v)[37 degrees C] = 0.713 +/- 0.018, mean +/- S.D. compared to 0.686 +/- 0.008 in the normal subjects, P < 0.001) and correlated significantly with the cholesterol/phospholipid ratio (r = 0.88, P < 0.001). The fluidity of lipid extracts from the membranes of patient erythrocytes was also decreased, suggesting that decreased membrane fluidity was mainly a consequence of altered lipid composition rather than protein abnormalities. Incubation of patient erythrocytes for 20 hr with normal, heated plasma removed the excess cholesterol without affecting the phosphatidylcholine/sphingomyelin ratio or phospholipid fatty acid composition; following incubation the fluidity of these membranes was similar to that of normal membranes. We conclude that in liver disease changes in the composition of the phospholipid bilayer matrix in the erythrocyte membrane have little influence on its fluidity; the reduced fluidity is predominantly a result of increases in cholesterol relative to phospholipid.-Owen, J. S., K. R. Bruckdorfer, R. C. Day, and N. McIntyre. Decreased erythrocyte membrane fluidity and altered lipid composition in human liver disease.