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Biologically active low density lipoprotein in human peripheral lymph.

D Reichl, N B Myant, M S Brown

    The Journal of Clinical Investigation
    |January 1, 1978
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    Summary
    This summary is machine-generated.

    Human serum and lymph both suppress cholesterol synthesis and activate ester formation. Lymph contains functional low-density lipoprotein (LDL) at about 1/10th the concentration found in serum.

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    Area of Science:

    • Biochemistry
    • Lipid Metabolism
    • Cell Biology

    Background:

    • Low-density lipoprotein (LDL) plays a crucial role in cholesterol transport and metabolism.
    • Understanding the presence and function of LDL in different biological fluids is essential for comprehending lipid homeostasis.
    • Familial hypercholesterolemia highlights the importance of LDL receptors in cholesterol regulation.

    Purpose of the Study:

    • To compare the biological activities of human serum and peripheral lymph concerning LDL metabolism.
    • To investigate the effects of lymph on 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity, cholesteryl ester synthesis, and LDL receptor binding.
    • To determine the concentration and functional characteristics of LDL in human lymph.

    Main Methods:

    • Cultured human fibroblasts were used to assess the effects of serum and lymph.
    • Assays were performed to measure HMG-CoA reductase activity and cholesteryl ester synthesis.
    • Competition assays with 125I-labeled LDL were conducted to evaluate binding to LDL receptors.
    • Ultracentrifugation was used to isolate lipoprotein fractions (d < 1.063 g/ml).
    • Fibroblasts from patients with homozygous familial hypercholesterolemia were utilized to assess LDL receptor-dependent activity.

    Main Results:

    • Whole lymph demonstrated activity in suppressing HMG-CoA reductase, activating cholesteryl ester synthesis, and competing for LDL receptor binding, similar to serum.
    • The biological activity in lymph was approximately 1/10th that of serum per unit volume.
    • All measured activities in lymph were localized to the fraction with a density less than 1.063 g/ml.
    • Lymph showed no significant effect on HMG-CoA reductase activity in cells lacking LDL receptors, confirming LDL-mediated action.
    • The LDL-like biologic activity per unit mass of apoprotein B was comparable in lymph and serum.

    Conclusions:

    • Functionally active low-density lipoprotein (LDL) is present in human peripheral lymph.
    • The concentration of active LDL in lymph is approximately 1/10th that found in serum.
    • These findings suggest that lymph contributes to cholesterol transport and metabolism, with LDL being a key component.