Abstract
We have compared the ability of human serum and peripheral lymph to suppress the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), to activate cholesteryl ester synthesis, and to compete with 125I-labeled low density lipoprotein (LDL) for binding to LDL receptors in cultured human fibroblasts. Whole lymph was active in all three tests and the activity per unit volume in lymph was approximately equal to 1/10th that in serum. All three biologic activities in lymph were confined to the d less than 1.063 g/ml fraction. Whole lymph had no significant effect on HMG-CoA reductase activity in fibroblasts from a patient with homozygous familial hypercholesterolemia, whose cells lack LDL receptors. The LDL-like biologic activity per unit mass of immunologically active apoprotein B was approximately the same in lymph as in serum. The current data indicate that functionally active LDL is present in lymph and that the concentration of this lipoprotein is approximately equal to 1/10th that in serum.
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Selected References
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- Bersot T. P., Mahley R. W., Brown M. S., Goldstein J. L. Interaction of swine lipoproteins with the low density lipoprotein receptor in human fibroblasts. J Biol Chem. 1976 Apr 25;251(8):2395–2398. [PubMed] [Google Scholar]
- Blomhoff J. P. Serum cholesterol determination by gas-liquid chromatography. Clin Chim Acta. 1973 Jan 24;43(2):257–265. doi: 10.1016/0009-8981(73)90459-2. [DOI] [PubMed] [Google Scholar]
- Brown M. S., Dana S. E., Goldstein J. L. Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in cultured human fibroblasts. Comparison of cells from a normal subject and from a patient with homozygous familial hypercholesterolemia. J Biol Chem. 1974 Feb 10;249(3):789–796. [PubMed] [Google Scholar]
- Brown M. S., Goldstein J. L. Familial hypercholesterolemia: A genetic defect in the low-density lipoprotein receptor. N Engl J Med. 1976 Jun 17;294(25):1386–1390. doi: 10.1056/NEJM197606172942509. [DOI] [PubMed] [Google Scholar]
- Brown M. S., Goldstein J. L. Familial hypercholesterolemia: defective binding of lipoproteins to cultured fibroblasts associated with impaired regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. Proc Natl Acad Sci U S A. 1974 Mar;71(3):788–792. doi: 10.1073/pnas.71.3.788. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brown M. S., Goldstein J. L. Receptor-mediated control of cholesterol metabolism. Science. 1976 Jan 16;191(4223):150–154. doi: 10.1126/science.174194. [DOI] [PubMed] [Google Scholar]
- Brown M. S., Goldstein J. L. Suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and inhibition of growth of human fibroblasts by 7-ketocholesterol. J Biol Chem. 1974 Nov 25;249(22):7306–7314. [PubMed] [Google Scholar]
- GROTTE G. Passage of dextran molecules across the blood-lymph barrier. Acta Chir Scand Suppl. 1956;211:1–84. [PubMed] [Google Scholar]
- Goldstein J. L., Basu S. K., Brunschede G. Y., Brown M. S. Release of low density lipoprotein from its cell surface receptor by sulfated glycosaminoglycans. Cell. 1976 Jan;7(1):85–95. doi: 10.1016/0092-8674(76)90258-0. [DOI] [PubMed] [Google Scholar]
- Goldstein J. L., Brown M. S. Binding and degradation of low density lipoproteins by cultured human fibroblasts. Comparison of cells from a normal subject and from a patient with homozygous familial hypercholesterolemia. J Biol Chem. 1974 Aug 25;249(16):5153–5162. [PubMed] [Google Scholar]
- Goldstein J. L., Brown M. S. The LDL pathway in human fibroblasts: a receptor-mediated mechanism for the regulation of cholesterol metabolism. Curr Top Cell Regul. 1976;11:147–181. doi: 10.1016/b978-0-12-152811-9.50011-0. [DOI] [PubMed] [Google Scholar]
- Goldstein J. L., Brown M. S. The low-density lipoprotein pathway and its relation to atherosclerosis. Annu Rev Biochem. 1977;46:897–930. doi: 10.1146/annurev.bi.46.070177.004341. [DOI] [PubMed] [Google Scholar]
- Goldstein J. L., Dana S. E., Brown M. S. Esterification of low density lipoprotein cholesterol in human fibroblasts and its absence in homozygous familial hypercholesterolemia. Proc Natl Acad Sci U S A. 1974 Nov;71(11):4288–4292. doi: 10.1073/pnas.71.11.4288. [DOI] [PMC free article] [PubMed] [Google Scholar]
- HAVEL R. J., EDER H. A., BRAGDON J. H. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest. 1955 Sep;34(9):1345–1353. doi: 10.1172/JCI103182. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Havel R. J., Kane J. P. Primary dysbetalipoproteinemia: predominance of a specific apoprotein species in triglyceride-rich lipoproteins. Proc Natl Acad Sci U S A. 1973 Jul;70(7):2015–2019. doi: 10.1073/pnas.70.7.2015. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ho Y. K., Brown S., Bilheimer D. W., Goldstein J. L. Regulation of low density lipoprotein receptor activity in freshly isolated human lymphocytes. J Clin Invest. 1976 Dec;58(6):1465–1474. doi: 10.1172/JCI108603. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jackson R. L., Morrisett J. D., Gotto A. M., Jr Lipoprotein structure and metabolism. Physiol Rev. 1976 Apr;56(2):259–316. doi: 10.1152/physrev.1976.56.2.259. [DOI] [PubMed] [Google Scholar]
- Kailis S. G., Morgan E. H. Transferrin and iron uptake by rabbit bone marrow cells in vitro. Br J Haematol. 1974 Sep;28(1):37–52. doi: 10.1111/j.1365-2141.1974.tb06638.x. [DOI] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Mahley R. W., Innerarity T. L. Interaction of canine and swine lipoproteins with the low density lipoprotein receptor of fibroblasts as correlated with heparin/manganese precipitability. J Biol Chem. 1977 Jun 10;252(11):3980–3986. [PubMed] [Google Scholar]
- Reichl D., Myant N. B., Pflug J. J. Concentration of lipoproteins containing apolipoprotein B in human peripheral lymph. Biochim Biophys Acta. 1977 Oct 24;489(1):98–105. doi: 10.1016/0005-2760(77)90236-3. [DOI] [PubMed] [Google Scholar]
- Reichl D., Postiglione A., Myant N. B., Pflug J. J., Press M. Observations on the passage of apoproteins from plasma lipoproteins into peripheral lymph in two men. Clin Sci Mol Med. 1975 Nov;49(5):419–426. doi: 10.1042/cs0490419. [DOI] [PubMed] [Google Scholar]
- Reichl D., Simons L. A., Myant N. B., Pflug J. J., Mills G. L. The lipids and lipoproteins of human peripheral lymph, with observations on the transport of cholesterol from plasma and tissues into lymph. Clin Sci Mol Med. 1973 Sep;45(3):313–329. doi: 10.1042/cs0450313. [DOI] [PubMed] [Google Scholar]
- Schneider R. J., Burger R. L., Mehlman C. S., Allen R. H. The role and fate of rabbit and human transcobalamin II in the plasma transport of vitamin B12 in the rabbit. J Clin Invest. 1976 Jan;57(1):27–38. doi: 10.1172/JCI108265. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shelburne F. A., Quarfordt S. H. A new apoprotein of human plasma very low density lipoproteins. J Biol Chem. 1974 Mar 10;249(5):1428–1433. [PubMed] [Google Scholar]
