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. 1975 Mar;55(3):636–643. doi: 10.1172/JCI107971

Platelet hypersensitivity induced by cholesterol incorporation.

S J Shattil, R Anaya-Galindo, J Bennett, R W Colman, R A Cooper
PMCID: PMC301792  PMID: 1117069

Abstract

Platelets from individuals with familial hypercholesterolemia show increased sensitivity to the aggregating atents, epinephrine and ADP. Since the mechanism of this abnormal sensitivity is unknown, we examined, in vitro, the influence of the plasma lipid environment on the function of platelets. The composition of plasma lipids was altered by the addition of sonicated cholesterol-dipalmitoyl lecithin liposomes which were "cholesterol normal" (cholesterol-phospholipid mole ratio [C/P] equals 1.0, "cholesterol rich" (C/P eauals 2.2), or "cholesterol poor" (C/P equals 0). Cholesterol-normal liposomes had no influence on platelet lipids or platelet function. In contrast, after incubation for 5 h at 37 degrees C with cholesterol-rich liposomes, normal platelets acquired 39.2% excess cholesterol with no change in phospholipids or protein. The percent increase in platelet membrane cholesterol was three-fold that of the granule fraction. The acquisition of cholesterol by platelets was associated with a 35-fold increase in sensitivity to epinephrine-induced aggregation (P less than 0.001) and 15-fold increase to ADP aggregation (P less than 0.001), as determined both by aggregometry and by [13C]serotonin release. Response to thrombin or collagen was unchanged. Platelets incubated with cholesterol-poor liposomes underwent a selective loss of 21.4% cholesterol and this was associated with an 18-fold reduction in their sensitivity to epinephrine. These studies demonstrate that the cholesterol content of platelets is dependent on the lipid composition of the milier. Cholesterol acquired by platelets may exert its effect on platelet function by a modification of the platelet membrane.

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Selected References

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

  1. BARTLETT G. R. Phosphorus assay in column chromatography. J Biol Chem. 1959 Mar;234(3):466–468. [PubMed] [Google Scholar]
  2. BORN G. V. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature. 1962 Jun 9;194:927–929. doi: 10.1038/194927b0. [DOI] [PubMed] [Google Scholar]
  3. Bolton C. H., Hampton J. R., Mitchell J. R. Nature of the transferable factor which causes abnormal platelet behaviour in vascular disease. Lancet. 1967 Nov 25;2(7526):1101–1105. doi: 10.1016/s0140-6736(67)90614-9. [DOI] [PubMed] [Google Scholar]
  4. Bull B. S., Schneiderman M. A., Brecher G. Platelet counts with the Coulter counter. Am J Clin Pathol. 1965 Dec;44(6):678–688. doi: 10.1093/ajcp/44.6.678. [DOI] [PubMed] [Google Scholar]
  5. Carvalho A. C., Colman R. W., Lees R. S. Platelet function in hyperlipoproteinemia. N Engl J Med. 1974 Feb 21;290(8):434–438. doi: 10.1056/NEJM197402212900805. [DOI] [PubMed] [Google Scholar]
  6. Cooper R. A. Anemia with spur cells: a red cell defect acquired in serum and modified in the circulation. J Clin Invest. 1969 Oct;48(10):1820–1831. doi: 10.1172/JCI106148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cooper R. A., Arner E. C., Wiley J. S., Shattil S. J. Modification of red cell membrane structure by cholesterol-rich lipid dispersions. A model for the primary spur cell defect. J Clin Invest. 1975 Jan;55(1):115–126. doi: 10.1172/JCI107901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cooper R. A., Kimball D. B., Durocher J. R. Role of the spleen in membrane conditioning and hemolysis of spur cells in liver disease. N Engl J Med. 1974 Jun 6;290(23):1279–1284. doi: 10.1056/NEJM197406062902303. [DOI] [PubMed] [Google Scholar]
  9. Fishman W. H., Kato K., Anstiss C. L., Green S. Human serum beta-glucuronidase; its measurement and some of its properties. Clin Chim Acta. 1967 Mar;15(3):435–447. doi: 10.1016/0009-8981(67)90008-3. [DOI] [PubMed] [Google Scholar]
  10. French J. E. Atherogenesis and thrombosis. Semin Hematol. 1971 Jan;8(1):84–94. [PubMed] [Google Scholar]
  11. GAINTNER J. R., JACKSON D. P., MAYNERT E. W. The action of thromb in on platelet 5-hydroxytryptamine. Bull Johns Hopkins Hosp. 1962 Oct;111:185–197. [PubMed] [Google Scholar]
  12. 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]
  13. Hampton J. R., Mitchell J. R. A transferable factor causing abnormal platelet behaviour in vascular disease. Lancet. 1966 Oct 8;2(7467):764–768. doi: 10.1016/s0140-6736(66)90362-x. [DOI] [PubMed] [Google Scholar]
  14. Jerushalmy Z., Zucker M. B. Some effects of fibrinogen degradation products (FDP) on blood platelets. Thromb Diath Haemorrh. 1966 May 15;15(3):413–419. [PubMed] [Google Scholar]
  15. Kannel W. B., Castelli W. P., McNamara P. M. The coronary profile: 12-year follow-up in the Framingham study. J Occup Med. 1967 Dec;9(12):611–619. [PubMed] [Google Scholar]
  16. 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]
  17. Marcus A. J., Ullman H. L., Safier L. B. Lipid composition of subcellular particles of human blood platelets. J Lipid Res. 1969 Jan;10(1):108–114. [PubMed] [Google Scholar]
  18. Marcus A. J., Zucker-Franklin D., Safier L. B., Ullman H. L. Studies on human platelet granules and membranes. J Clin Invest. 1966 Jan;45(1):14–28. doi: 10.1172/JCI105318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mustard J. F., Perry D. W., Ardlie N. G., Packham M. A. Preparation of suspensions of washed platelets from humans. Br J Haematol. 1972 Feb;22(2):193–204. doi: 10.1111/j.1365-2141.1972.tb08800.x. [DOI] [PubMed] [Google Scholar]
  20. Nordoy A., Rodset J. M. Platelet phospholipids and their function in patients with ishemic heart disease. Acta Med Scand. 1970 Jul-Aug;1-2(1):133–137. [PubMed] [Google Scholar]
  21. Oldfield E., Chapman D. Dynamics of lipids in membranes: Heterogeneity and the role of cholesterol. FEBS Lett. 1972 Jul 1;23(3):285–297. doi: 10.1016/0014-5793(72)80300-4. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Rosenberg R. D., Waugh D. F. Multiple bovine thrombin components. J Biol Chem. 1970 Oct 10;245(19):5049–5056. [PubMed] [Google Scholar]
  24. Rudel L. L., Morris M. D. Determination of cholesterol using o-phthalaldehyde. J Lipid Res. 1973 May;14(3):364–366. [PubMed] [Google Scholar]
  25. Shinitzky M., Inbar M. Difference in microviscosity induced by different cholesterol levels in the surface membrane lipid layer of normal lymphocytes and malignant lymphoma cells. J Mol Biol. 1974 Jan 5;85(4):603–615. doi: 10.1016/0022-2836(74)90318-0. [DOI] [PubMed] [Google Scholar]
  26. Skipski V. P., Peterson R. F., Barclay M. Quantitative analysis of phospholipids by thin-layer chromatography. Biochem J. 1964 Feb;90(2):374–378. doi: 10.1042/bj0900374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Taylor D. G., Crawford N. The subfractionation of platelet membranes by zonal centrifugation: identification of surface membranes. FEBS Lett. 1974 May 1;41(2):317–322. doi: 10.1016/0014-5793(74)81238-x. [DOI] [PubMed] [Google Scholar]
  28. Vanderkooi J., Fischkoff S., Chance B., Cooper R. A. Fluorescent probe analysis of the lipid architecture of natural and experimental cholesterol-rich membranes. Biochemistry. 1974 Apr 9;13(8):1589–1595. doi: 10.1021/bi00705a006. [DOI] [PubMed] [Google Scholar]
  29. WROBLEWSKI F., LADUE J. S. Lactic dehydrogenase activity in blood. Proc Soc Exp Biol Med. 1955 Oct;90(1):210–213. doi: 10.3181/00379727-90-21985. [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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