Detection of erythrocyte membrane structural abnormalities in lecithin: Cholesterol acyltransferase deficiency using a spin label approach

Abstract

The membrane fluidity of erythrocytes from patients with Lecithin: cholesterol acyltransferase (LCAT) deficiency was studied by means of electron spin resonance. The temperature dependence of the separation of the outer extrema of the spectra of 2-(3-carboxy-propyl)-4,4-dimethyl, 2-tridecyl-3-oxazolidinyloxyl spin probe was monitored for normal, presumed carrier and clinically affected subjects. The temperature profile of controls was significantly different from that of the presumed carriers and the clinically affected individuals. The results show that the compositional abnormalities previously noted in erythrocyte membranes from patients with LCAT deficiency are associated with alterations in the physiocochemical state of the membrane. An investigation of the spectral lineshapes below 10 degrees C allowed a distinction to be made at the membrane level between clinically affected subjects and clinically normal heterozygous carriers. Alterations in the temperature dependence of elec-ron spin resonance parameters may provide a sensitive index of red cell membrane alterations in pathological states of generalized membrane involvement.

Spin label studies of erythrocytes with abnormal lipid composition: comparison of red cells in a hereditary hemolytic syndrome and lecithin: Cholesterol acyltransferase deficiency

“…This alteration, which was also present in the erythrocyte membranes of individuals with LCAT deficiency [13], indicated a more fluid membrane. The profiles of the patients were parallel to the control curve up to about 30"C, at which temperature there was an inflection with the membranes of the experimental subjects approaching the same fluidity as the control samples at 34°C.…”

“…The magnitude of these fluidity changes, however, is somewhat less than might have been expected from the phospholipid abnormalities. In the case of LCAT deficiency [13], the increased levels of membrane cholesterol would likely exert a rigidifying influence [9, 1 11 and tend to minimize the increase in fluidity produced by the marked elevation in membrane PC and possibly the decrease in phosphatidylethanolamine (Table I).…”

Prebiotic Oligosaccharides Potentiate Host Protective Responses against L. Monocytogenes Infection

“…LCAT and PLA2G3 are both involved in the phospholipid signaling pathway. Changes in LCAT abundance can result in modulation of host membrane fluidity and cholesterol concentration while PLA2G3 is a member of secreted phospholipase A2 family with protective activity against microbial pathogens [ 60 , 61 , 62 ]. The finding of these two uniquely differentially expressed genes in HMO/+Lm provides additional evidence of HMO-induced alterations to the colonic cell surface and subsequent signaling cascades.…”