Fluidity properties and liquid composition of erythrocyte membranes in Chediak-Higashi syndrome.

Abstract

We have earlier shown through electron spin resonance (ESR) studies of leukocytes that membranes of cells from both Chediak-Higashi syndrome (CHS) mice and humans have abnormally high fluidity . We have extended our studies to erythrocytes . Erythrocytes were labeled with the nitroxide-substituted analogue of stearic acid, 2-(3-carboxypropyl)-4,4-dimethyl-2-tridecyl-3-oxazolidinyloxyl, and ESR spectra were obtained . Order parameter, S, at 23°C, was 0.661 and 0.653 for erythrocytes of normal and CHS mice (P < 0.001) . S was 0.684 for normal human erythrocytes and 0.675 (P < 0.001) for CHS erythrocytes at 25°C. Because S varies inversely to fluidity, these results indicate that CHS erythrocytes tend to have higher fluidity than normal . In vitro treatment of both mice and human CHS erythrocytes with 10 mM ascorbate returned their membrane fluidity to normal . We prepared erythrocyte ghosts and extracted them with CHC1 3:CH3OH (2 :1) . Gas-liquid chromatography analysis showed a greater number of unsaturated fatty acids for CHS . The average number of double bonds detected in fatty acids for mice on a standard diet was 1 .77 for normal and 2.02 for CHS (P < 0.04) ; comparison of human erythrocytes from one normal control and one CHS patient showed a similar trend . Our results suggest that an increased proportion of unsaturated fatty acids may contribute to increased fluidity of CHS erythrocytes . Our observation that both leukocytes and erythrocytes of CHS have abnormal fluidity indicates that CHS pathophysiology may relate to a general membrane disorder.

The increase of cell-membranous phosphatidylcholines containing polyunsaturated fatty acid residues induces phosphorylation of p53 through activation of ATR

“…Many studies have demonstrated that modification of the polyunsaturated fatty acid composition of mammalian membranes alters their fluidity and function (Stubbs and Smith, 1984;Zamaria, 2004). Interestingly, the membranes of erythrocytes from both mice and humans with ChediakHigashi Syndrome (CHS) are abnormally fluid (Haak et al, 1979;Ingraham et al, 1981). The proportions of PCs(18:2) in these membranes are also elevated to levels comparable with those seen when iPLA 2 is inhibited.…”

Membrane Fluid Properties of Cord Blood Mononuclear Leucocytes: Association with Increased Insulin Receptors

“…Increasing membrane fluidity results from increasing the freedom of molecular motion and has been observed in several situations where lipid composition has been altered: 1)decreasing the cholesterol content relative to the amount of phospholipid; 2) increasing the phospholipid content relative to the amount of protein; 3) increasing the phosphotidylcholine content relative to sphingomyelin; 4) increasing the phosphatidylethanolamine content relative to phosphatidylcholine; 5) increasing the degree of unsaturation of fatty acids; and 6) decreasing the fatty acid chain length (22). From our data, it appears that the reduction in membrane fluidity of cord cells is due primarily to diminished phospholipid/protein ratios, which are also associated with increased cholesterol/phospholipid molar ratios relative to those of adult cells.…”

Use of fluorescence to determine the effects of cholesterol on lipid behavior in sphingomyelin liposomes and erythrocyte membranes

“…In an effort to provide some additional basis for interpretation of the data in Figs. 10 and 11, we created liposomes containing lipids representative of the outer or inner leaflets of the erythrocyte membrane (34,35) and repeated the measurements with DPH and laurdan at both high and low cholesterol concentrations. As shown in Fig.…”