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. 1968 Apr;47(4):809–822. doi: 10.1172/JCI105775

Bile salts and cholesterol in the pathogenesis of target cells in obstructive jaundice

Richard A Cooper 1, James H Jandl 1
PMCID: PMC297231  PMID: 5641620

Abstract

Free cholesterol is in rapid equilibrium between serum lipoproteins and red cells. The level of red cell cholesterol is influenced by bile salts, which shift the serum/cell partition of free cholesterol to the cell phase and which inhibit the cholesterol-esterifying mechanism. During incubation in normal serum possessing an active cholesterol-esterifying mechanism, red cells lose cholesterol and surface area and thereby become more spheroidal and less resistant to osmotic lysis. When exposed to serum from patients with obstructive jaundice or to normal serum with added bile salts, red cells accumulate cholesterol and increase their surface area, thereby acquiring a flattened shape and an increased resistance to osmotic lysis. The described gains and losses of red cell cholesterol and surface area do not involve metabolic injury and occur with no significant change in phospholipid content.

The red cells of patients with obstructive jaundice are flat and osmotically resistant and have an increased cholesterol:phospholipid ratio. When transfused into normal subjects these “target cells” rapidly lose their osmotic resistance. Similarly, normal cells acquire osmotic resistance in the circulation of patients with obstructive jaundice. These reversible changes in shape occur with half-times of about 9 and 24 hr, respectively, and occur without impairing cell viability.

These studies indicate that the red cell membrane accumulates cholesterol in obstructive jaundice as a consequence of the elevated levels of bile salts. The resulting increment in red cell surface area is responsible for the physical properties and appearance of target cells. These observations substantiate Murphy's findings in vitro indicating that cholesterol is an important determinant of red cell shape and that its content in the cell membrane may vary independently from the phospholipids. Presumably any process or disorder affecting cholesterol exchange in vivo is capable of critically modifying the shape and behavior of red cells.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BASFORD J. M., GLOVER J., GREEN C. EXCHANGE OF CHOLESTEROL BETWEEN HUMAN BETA-LIPOPROTEINS AND ERYTHROCYTES. Biochim Biophys Acta. 1964 Dec 2;84:764–766. doi: 10.1016/0926-6542(64)90039-3. [DOI] [PubMed] [Google Scholar]
  2. Bar R. S., Deamer D. W., Cornwell D. G. Surface area of human erythrocyte lipids: reinvestigation of experiments on plasma membrane. Science. 1966 Aug 26;153(3739):1010–1012. doi: 10.1126/science.153.3739.1010. [DOI] [PubMed] [Google Scholar]
  3. CAREY J. B., Jr The serum trihydroxy-dihydroxy bile acid ratio in liver and biliary tract disease. J Clin Invest. 1958 Nov;37(11):1494–1503. doi: 10.1172/JCI103741. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. DODGE J. T., MITCHELL C., HANAHAN D. J. The preparation and chemical characteristics of hemoglobin-free ghosts of human erythrocytes. Arch Biochem Biophys. 1963 Jan;100:119–130. doi: 10.1016/0003-9861(63)90042-0. [DOI] [PubMed] [Google Scholar]
  5. FELS G., KANABROCKI E., KAPLAN E. Plasma and red cell cholesterol. Clin Chem. 1961 Feb;7:16–21. [PubMed] [Google Scholar]
  6. FORMIJNE P., POULIE N. J., RODBARD J. A. Determination of phospholipid fractions in the human erythrocyte. Clin Chim Acta. 1957 Feb;2(1):25–34. doi: 10.1016/0009-8981(57)90021-9. [DOI] [PubMed] [Google Scholar]
  7. GLOMSET J. A. FURTHER STUDIES OF THE MECHANISM OF THE PLASMA CHOLESTEROL ESTERIFICATION REACTION. Biochim Biophys Acta. 1963 Aug 27;70:389–395. doi: 10.1016/0006-3002(63)90768-6. [DOI] [PubMed] [Google Scholar]
  8. GLOMSET J. A. The mechanism of the plasma cholesterol esterification reaction: plasma fatty acid transferase. Biochim Biophys Acta. 1962 Nov 19;65:128–135. doi: 10.1016/0006-3002(62)90156-7. [DOI] [PubMed] [Google Scholar]
  9. GOULD R. G., LEROY G. V., OKITA G. T., KABARA J. J., KEEGAN P., BERGENSTAL D. M. The use of C14-labeled acetate to study cholesterol metabolism in man. J Lab Clin Med. 1955 Sep;46(3):372–384. [PubMed] [Google Scholar]
  10. Goodman D. S. Cholesterol ester metabolism. Physiol Rev. 1965 Oct;45(4):747–839. doi: 10.1152/physrev.1965.45.4.747. [DOI] [PubMed] [Google Scholar]
  11. HAGERMAN J. S., GOULD R. G. The in vitro interchange of cholesterol between plasma and red cells. Proc Soc Exp Biol Med. 1951 Oct;78(1):329–332. doi: 10.3181/00379727-78-19064. [DOI] [PubMed] [Google Scholar]
  12. HARRIS J. W., SCHILLING R. F. Increased resistance to osmotic lysis as an acquired change in the erythrocytes of patients with hepatogenous jaundice or biliary obstruction. J Clin Invest. 1950 Jun;29(6):820–820. [PubMed] [Google Scholar]
  13. JANDL J. H. The anemia of liver disease: observations on its mechanism. J Clin Invest. 1955 Mar;34(3):390–404. doi: 10.1172/JCI103087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jacob H. S. Abnormalities in the physiology of the erythrocyte membrane in hereditary spherocytosis. Am J Med. 1966 Nov;41(5):734–743. doi: 10.1016/0002-9343(66)90034-9. [DOI] [PubMed] [Google Scholar]
  15. Korn E. D. Structure of biological membranes. Science. 1966 Sep 23;153(3743):1491–1498. doi: 10.1126/science.153.3743.1491. [DOI] [PubMed] [Google Scholar]
  16. LONDON I. M., SCHWARZ H. Erythrocyte metabolism; the metabolic behavior of the cholesterol of human erythrocytes. J Clin Invest. 1953 Dec;32(12):1248–1252. doi: 10.1172/JCI102853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Levy R. I., Fredrickson D. S., Laster L. The lipoproteins and lipid transport in abetalipoproteinemia. J Clin Invest. 1966 Apr;45(4):531–541. doi: 10.1172/JCI105367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. MURPHY J. R. ERYTHROCYTE METABOLISM. VI. CELL SHAPE AND THE LOCATION OF CHOLESTEROL IN THE ERYTHROCYTE MEMBRANE. J Lab Clin Med. 1965 May;65:756–774. [PubMed] [Google Scholar]
  19. Maddy A. H., Malcolm B. R. Protein conformations in the plasma membrane. Science. 1965 Dec 17;150(3703):1616–1618. doi: 10.1126/science.150.3703.1616. [DOI] [PubMed] [Google Scholar]
  20. PHILLIPS G. B. Quantitative chromatographic analysis of plasma and red blood cell lipids in patients with acanthocytosis. J Lab Clin Med. 1962 Mar;59:357–363. [PubMed] [Google Scholar]
  21. ROSE H. G., OKLANDER M. IMPROVED PROCEDURE FOR THE EXTRACTION OF LIPIDS FROM HUMAN ERYTHROCYTES. J Lipid Res. 1965 Jul;6:428–431. [PubMed] [Google Scholar]
  22. ROWEN R., MARTIN J. ENHANCEMENT OF CHOLESTEROL ESTERIFICATION IN SERUM BY AN EXTRACT OF GROUP-A STREPTOCOCCUS. Biochim Biophys Acta. 1963 Aug 27;70:396–405. doi: 10.1016/0006-3002(63)90769-8. [DOI] [PubMed] [Google Scholar]
  23. RUSS E. M., EDER H. A., BARR D. P. Protein-lipid relationships in human plasma. I. In normal individuals. Am J Med. 1951 Oct;11(4):468–479. doi: 10.1016/0002-9343(51)90182-9. [DOI] [PubMed] [Google Scholar]
  24. Reed C. F., Swisher S. N. Erythrocyte lipid loss in hereditary spherocytosis. J Clin Invest. 1966 May;45(5):777–781. doi: 10.1172/JCI105392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. SANDBERG D. H., SJOEVALL J., SJOEVALL K., TURNER D. A. MEASUREMENT OF HUMAN SERUM BILE ACIDS BY GAS-LIQUID CHROMATOGRAPHY. J Lipid Res. 1965 Apr;6:182–192. [PubMed] [Google Scholar]
  26. SAVITZ D., SIDEL V. W., SOLOMON A. K. OSMOTIC PROPERTIES OF HUMAN RED CELLS. J Gen Physiol. 1964 Sep;48:79–94. doi: 10.1085/jgp.48.1.79. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. TURNER K. B., McCORMACK G. H., Jr, RICHARDS A. The cholesterol-esterifying enzyme of human serum. I. In liver disease. J Clin Invest. 1953 Sep;32(9):801–806. doi: 10.1172/JCI102795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. WAYS P., REED C. F., HANAHAN D. J. RED-CELL AND PLASMA LIPIDS IN ACANTHOCYTOSIS. J Clin Invest. 1963 Aug;42:1248–1260. doi: 10.1172/JCI104810. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Weed R. I., Reed C. F. Membrane alterations leading to red cell destruction. Am J Med. 1966 Nov;41(5):681–698. doi: 10.1016/0002-9343(66)90030-1. [DOI] [PubMed] [Google Scholar]
  30. ZLATKIS A., ZAK B., BOYLE A. J. A new method for the direct determination of serum cholesterol. J Lab Clin Med. 1953 Mar;41(3):486–492. [PubMed] [Google Scholar]

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