Membrane Lipid Depletion in Hyperpermeable Red Blood Cells: Its Role in the Genesis of Spherocytes in Hereditary Spherocytosis*

Jacob, Harry S.

doi:10.1172/jci105695

Cited by 46 publications

(25 citation statements)

References 30 publications

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“…In contrast to this selective loss of red cell cholesterol, two recent studies have shown that red cells incubated in vitro lose both cholesterol and phospholipid, that they are lost in equivalent amounts, and that more is lost from hereditary spherocytosis (HS) than from normal red cells (9,10,17). HS cells are of particular interest because of their inordinate susceptibility to splenic pool- 906 The Journal of Clinical Investigation Volume 48 1969 ing exposing them to the conditions of erythrostasis (18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

The selective and conjoint loss of red cell lipids

Cooper¹,

Jandl²

1969

J. Clin. Invest.

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A B S T R A C T The pattern of lipid loss from the membrane of red cells incubated in serum is influenced by the availability of glucose. Under homeostatic conditions with respect to glucose, cholesterol alone is lost. This results from esterification of free cholesterol in serum by the serum enzyme, lecithin: cholesterol acyltransferase, and is associated with a proportional decrease in membrane surface area, reflected by an increased osmotic fragility. This selective loss of membrane cholesterol also occurs in hereditary spherocytosis (HS) red cells, even after incubation for 65 hr in the presence of glucose. The loss of free cholesterol from red cells relative to its loss from serum, under these conditions, is greatest at higher hematocrits, similar to those found in the spleen.Although the selective loss of membrane cholesterol increases the spherodicity of normal red cells, it does not lead to a change in their rate of glucose consumption, and both the loss of cholesterol and the increase in osmotic fragility are reversible in vitro. Moreover, normal red cells made osmotically fragile by cholesterol depletion in vitro rapidly become osmotically normal and survive normally after their reinfusion in vivo.In contrast to this selective loss of membrane cholesterol, red cells incubated in the absence of glucose lose both cholesterol and phospholipid. This occurs more rapidly in HS than normal red cells and is followed by a disruption of cation gradients and then by hemolysis. Cholesterol and phospholipid lost under these conditions is not restored during subsequent incubations in vitro.Selective loss of membrane cholesterol is a physiologic event secondary to an altered state of serum lipids. It is reversible both in vitro and in vivo and neither influences cellular metabolism nor impairs viability. ConThis work was presented in part at the Annual Meeting of the American Society of Hematology, December, 1967, and published in abstract form (1, 2).

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Section: Introductionmentioning

confidence: 99%

The selective and conjoint loss of red cell lipids

Cooper¹,

Jandl²

1969

J. Clin. Invest.

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“…Jacob (13) has also suggested that the greater phospholipid turnover in HS RBC, as measured by 82p incorporation, is causally related to the loss of lipid and membrane fragmentation which these cells undergo. Previous work from this laboratory (11,12) has suggested that premature alteration in the physical properties of the membrane protein in HS RBC resulting from ATP depletion was the critical factor in producing loss of membrane substance in these cells.…”

Section: Resultsmentioning

confidence: 99%

“…They 'report that the labeling of PS is increased by a factor of about two in the erythrocytes of patients with hereditary spherocytosis (HS RBC). They suggest that this increase is due to the greater rate of Na+ transport in these cells, and that this increased phospholipid turnover is responsible for the loss of lipid and membrane fragmentation found in HS RBC (11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Incorporation of orthophosphate-32P into erythrocyte phospholipids in normal subjects and in patients with hereditary spherocytosis

Reed¹

1968

J. Clin. Invest.

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A B S T R A C T The in vitro incorporation of inorganic 32P into erythrocyte phospholipids has been studied in normal subjects and in splenectomized patients with hereditary spherocytosis (HS). Phosphatidic acid (PA) was the only lipid measurably labeled in both kinds of cells. The actual turnover rate of PA phosphate was determined by simultaneously isolating inorganic phosphate (PI) and adenosine triphosphate (ATP) and determining their specific activities. This turnover is very small: 1.3 ,umoles P/liter of erythrocytes per hr in normal cells and 4.0 Mmoles P in HS erythrocytes when either ATP or cellular Pi is considered the immediate precursor. This value represents less than 0.1% of the total membrane lipid phosphate. Incorporation of added 32P1 into the other phosphatides, including phosphatidyl serine, was essentially zero in both kinds of cells.The effects of stimulation and inhibition of active cation transport, metabolic depletion, and extracellular phosphate concentration on both the degree of labeling and the actual turnover of PA phosphate were studied. In any given experiment, the degree of labeling of PA depended on the specific activities of the other intracellular phosphates (Pi and ATP). The actual turnover rate of PA phosphate, however, did not vary with active transport or metabolic depletion. The greater turnover of PA phosphate in HS erythrocytes may be due to the somewhat younger age of these cells. TheReceived for publication 8 July 1968 and in revised form 12 Au ngust 1968. results suggest that the very low turnover of PA phosphate in erythrocytes is mediated by nonspecific enzyme reactions, and that it is quantitatively insignificant in both normal and HS erythrocytes. The results also emphasize the importance of measuring intracellular phosphate precursors in any study evaluating cellular phospholipid turnover from added 32P,.

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“…However, spherical red cells. 4 Decrease in OF (more resistant to hemolysis) OFT may not be an effective screening technique in the areas has been observed in thalassemia, iron deficiency, some forms of where iron deficiency is prevalent, such as in Egypt. 14 In spite of liver diseases and lead poisoning.…”

Section: Introductionmentioning

confidence: 99%

A Stopped Flow System with Hydrodynamic Injection for Red Blood Cells Osmotic Fragility Test: Possibility for Automatic Screening of Beta-thalassemia Trait

et al. 2009

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Simple instrumentation and procedure with stopped flow system coupled to hydrodynamic injection and spectrophotometric detection were developed for automatic osmotic fragility test (OFT). OFT is a test for abnormal red blood cells based on the kinetics of their rupturing in a hypotonic saline solution. A portion of red cells was merged on-line with a hypotonic saline solution. They were mixed while flowing into the detector and were stopped for a short period for continuously monitoring the change of turbidity based on a transmission signal. In this work, a possible application of the system for screening of beta-thalassemia trait is demonstrated. Descriptions of instrumentation development and parameter optimization are presented. The system offers advantages over the conventional batch-wise OFT in terms of automation, precision, analysis time and sample volume.

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Membrane Lipid Depletion in Hyperpermeable Red Blood Cells: Its Role in the Genesis of Spherocytes in Hereditary Spherocytosis*

Cited by 46 publications

References 30 publications

The selective and conjoint loss of red cell lipids

The selective and conjoint loss of red cell lipids

Incorporation of orthophosphate-32P into erythrocyte phospholipids in normal subjects and in patients with hereditary spherocytosis

A Stopped Flow System with Hydrodynamic Injection for Red Blood Cells Osmotic Fragility Test: Possibility for Automatic Screening of Beta-thalassemia Trait

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