Correlations between membrane viscosity, serum cholesterol, lymphocyte activation and aging in man

Rivnay, Benjamin; Bergman, Sarah; Shinitzky, Meir; Globerson, Amiela

doi:10.1016/0047-6374(80)90088-3

Cited by 155 publications

(29 citation statements)

References 34 publications

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“…An increased proportion o f cholesterol to phospholipids was observed in the lymphocyte membranes o f old mice [17] and humans [18]. These changes correlated with the in creased microviscosity of the membrane, and decreased re activity to mitogen stimulation.…”

Section: Lymphocyte Membrane Microviscositymentioning

confidence: 74%

T Lymphocytes and Aging

Globerson

1995

Int Arch Allergy Immunol

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Some of the key features of aging effects on T lymphocytes have been illuminated in the last few years from new angles. Experimental evidence indicates a profound increase in the proportion of memory versus naive types of T cells, a decline in the response to activation and in the capacity to enter the cycle, and decline in levels of IL-2, yet an increase in various other cytokines. At least part of these changes are based on altered patterns of T lymphocyte development. Long-term cultures of T cells from young donors show that certain manifestations of aging are acquired under such in vitro conditions. The T lymphocyte compartment thus offers a unique experimental model to investigate different checkpoints in development and function of the cells, as based on vulnerability to the effects of aging.

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Section: Lymphocyte Membrane Microviscositymentioning

confidence: 74%

T Lymphocytes and Aging

Globerson

1995

Int Arch Allergy Immunol

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“…The maintenance of a constant membrane lipid fluidity (microviscosity) within precisely determined limits has been identified as an indispensable necbssity for proper functioning of almost all types of cells [l-31. Loss of homeostatic control of membrane microviscosity is postulated to be responsible for the decline in immune function with age [4,5]. Changes in membrane microviscosity of human and murine lymphocytes have been shown to correlate with age-related changes in plasma lipid levels as well as with a decline of in vitro mitogen responsiveness [4].…”

Section: Introductionmentioning

confidence: 99%

Correlation of lymphocyte lipid composition membrane microviscosity and mitogen response in the aged

Huber¹,

Jürgens

et al. 1991

Eur J Immunol

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Healthy aged and young blood donors were investigated for the role of membrane lipid composition in the age-related increase in membrane microviscosity and decline of mitogen responsiveness. Membrane microviscosity was shown to correlate positively with membrane cholesterol/phospholipid molar ratios, which were significantly elevated in the elderly. A positive correlation also was confirmed between lymphocyte membrane microviscosity, which was measured using the probe 1,6-diphenyl 1,3,5-hexatriene, and phytohemagglutinin responsiveness of cells from the same donor. Using stepwise regression statistical analysis, the variables age, cholesterol, cholesterol/total phospholipid and phosphatidyl ethanolamine/phosphatidyl choline molar ratios were all shown to have a significant positive influence on membrane microviscosity, whereas total phospholipids had a negative effect. No statistically significant difference was seen in content of any single saturated or unsaturated fatty acid between young and old donors. After pooling, however, the proportion of all unsaturated fatty acids was significantly higher in cells from the elderly as a consequence of an increase of n-6 and n-3 polyunsaturated fatty acids. Changes in lipid composition and physical properties of lymphocyte plasma membranes may, therefore, be responsible (at least partially) for the diminution of immune reactivity in old age.

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“…Lymphocyte mitogenesis decreases during aging. 58 On the other hand, the LDL receptor activity of elderly people increases in lymphocytes. 59 Thus, taking into account our experience and information in the literature, monocytes are preferred for the detection of LDL receptor deficiences by flow cytometry.…”

Section: -51mentioning

confidence: 99%

Fluorescence flow cytometry of human leukocytes in the detection of LDL receptor defects in the differential diagnosis of hypercholesterolemia.

Schmitz

Brüning

Kovács

et al. 1993

Arterioscler Thromb

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A flow-cytometric method with fluorescence-labeled monoclonal antibodies (MABs) against the low density lipoprotein (LDL) receptor (C7A MAB) or 3,3'-dioctadecylindocarbocyanin-iodide (Dil) LDL has been developed that allows the quantification of LDL receptors on leukocytes and the identification of patients with familial hypercholesterolemia (FH) within 48 hours. Leukocytes were isolated from 10 mL anticoagulated blood by density gradient centrifugation. To induce maximal expression of LDL receptors, mononuclear cells were preincubated with either phytoheraagglutinine (PHA) or iipoprotein-deflcient serum (LPDS). LPDS-treated raonocytes provided a more homogeneous cell population with regard to LDL receptor activity than did the PHA-treated lymphocytes; they also provided a greater discrimination between the fluorescence of the receptor probes and cellular autofluorescence. The C7A MAB was able to compete for Dil LDL binding by about 40%. In competition with unlabeled LDL, Dil LDL revealed linear binding, indicating an affinity similar to native LDL. The binding characteristics of Dil LDL were also similar to IZ5 I-LDL binding. LDL isolated from familial defective apolipoprotein B-100 was not able to compete for Dil LDL binding on monocytes, whereas native LDL reduced it by about 80%. In monocytes from FH heterozygous patients, the cellular mean fluorescence using either C7A MAB or Dil LDL at 4°C was 30% to 70%; in FH homozygotes, cellular mean fluorescence was less than 20% of that in monocytes from normal individuals. In patients with familial defective apolipoprotein B-100 antibody binding was normal, but one patient's own LDL failed to compete with normal Dil LDL for 4°C binding on U937 test monocytes. Patient monocytes having internalization defects showed normal 4°C Dil LDL binding, but at 20°C cell-associated fluorescence was reduced by about 40%. In our study 384 hypercholesterolemic patients (preselected according to serum cholesterol levels, clinical symptoms, and family history) were analyzed for LDL receptor expression using the C7A MAB-based assay. In 71.8% of the patients with cholesterol levels higher than 300 mg/dL, an LDL receptor deficiency was observed. Apolipoprotein E isofonns and lipoprotein [a] were found to be independent from the LDL receptor status. In some patients with high cholesterol levels but normal LDL receptor expression with the C7A MAB assay, LDL receptor defects could be diagnosed when either reduced binding or internalization of Dil LDL or familial defective apolipoprotein B-100 was detected. We conclude that fluorescence flow cytometry provides an appropriate, easily performed assay system for the differential diagnosis of LDL receptor defects, including LDL receptor deficiencies and internalization defects, and also allows the discovery of ligand defects.

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Correlations between membrane viscosity, serum cholesterol, lymphocyte activation and aging in man

Cited by 155 publications

References 34 publications

T Lymphocytes and Aging

T Lymphocytes and Aging

Correlation of lymphocyte lipid composition membrane microviscosity and mitogen response in the aged

Fluorescence flow cytometry of human leukocytes in the detection of LDL receptor defects in the differential diagnosis of hypercholesterolemia.

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