Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1967 Nov;46(11):1715–1723. doi: 10.1172/JCI105662

Studies of Paroxysmal Nocturnal Hemoglobinuria Erythrocytes: Increased Lysis and Lipid Peroxide Formation by Hydrogen Peroxide*

Charles E Mengel 1,‡, Herbert E Kann Jr 1,§, Wilhelm D Meriwether 1,ǁ
PMCID: PMC292922  PMID: 6061745

Abstract

When paroxysmal nocturnal hemoglobinuria (PNH) erythrocytes were exposed to H2O2 they lysed excessively and formed greater than normal quantities of lipid peroxides when compared to red cells of normal subjects and patients with most types of hematologic disease. It was also shown that lytic sensitivity to acidified serum was related to the enhanced lytic sensitivity to H2O2. If the lipid of PNH cells was first extracted then exposed to ultraviolet radiation more lipid peroxides were formed than in extracts of normal red blood cells. The possible explanations for these findings and their relationship to the PNH hemolytic mechanism are discussed.

Full text

PDF
1715

Images in this article

1717Image
on p.1717

Selected References

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

  1. BAKER N., WILSON L. Inhibition of tumor glycolysis by hydrogen peroxide formed from autoxidation of unsaturated fatty acids. Biochem Biophys Res Commun. 1963 Apr 2;11:60–64. doi: 10.1016/0006-291x(63)90028-7. [DOI] [PubMed] [Google Scholar]
  2. BARRY R. M. The phospholipid distribution in the erythrocyte in paroxysmal nocturnal haemoglobinuria. Br J Haematol. 1959 Apr;5(2):212–216. doi: 10.1111/j.1365-2141.1959.tb04027.x. [DOI] [PubMed] [Google Scholar]
  3. BEUTLER E., DURON O., KELLY B. M. Improved method for the determination of blood glutathione. J Lab Clin Med. 1963 May;61:882–888. [PubMed] [Google Scholar]
  4. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  5. BRAUNSTEINER H., GISINGER E., PAKESCH F. Confirmation of a structural abnormity in the stroma of erythrocytes from paroxysmal nocturnal hemoglobinuria (PNH) after hemolysis in distilled water. Blood. 1956 Aug;11(8):753–756. [PubMed] [Google Scholar]
  6. Binder H. J., Herting D. C., Hurst V., Finch S. C., Spiro H. M. Tocopherol deficiency in man. N Engl J Med. 1965 Dec 9;273(24):1289–1297. doi: 10.1056/NEJM196512092732401. [DOI] [PubMed] [Google Scholar]
  7. CECCHI E., CONESTABILE E. Paroxysmal nocturnal haemoglobinuria; electronmicroscopic study of red blood-cells. Lancet. 1957 Sep 7;273(6993):466–468. doi: 10.1016/s0140-6736(57)90771-7. [DOI] [PubMed] [Google Scholar]
  8. CORNBLATH M., GORDON H. H., NITOWSKY H. M. Studies of tocopherol deficiency in infants and children. II. Plasma tocopherol and erythrocyte hemolysis in hydrogen peroxide. AMA J Dis Child. 1956 Aug;92(2):164–174. doi: 10.1001/archpedi.1956.02060030158010. [DOI] [PubMed] [Google Scholar]
  9. CROSBY W. H. Paroxysmal nocturnal hemoglobinuria; plasma factors of the hemolytic system. Blood. 1953 May;8(5):444–458. [PubMed] [Google Scholar]
  10. DE GIER J., VAN DEENENL, VERLOOP M. C., VAN GASTEL PHOSPHOLIPID AND FATTY ACID CHARACTERISTICS OF ERYTHROCYTES IN SOME CASES OF ANAEMIA. Br J Haematol. 1964 Apr;10:246–256. doi: 10.1111/j.1365-2141.1964.tb00699.x. [DOI] [PubMed] [Google Scholar]
  11. DE GIER J., VAN DEENENL, VERLOOP M. C., VAN GASTEL PHOSPHOLIPID AND FATTY ACID CHARACTERISTICS OF ERYTHROCYTES IN SOME CASES OF ANAEMIA. Br J Haematol. 1964 Apr;10:246–256. doi: 10.1111/j.1365-2141.1964.tb00699.x. [DOI] [PubMed] [Google Scholar]
  12. DESAI I. D., TAPPEL A. L. DAMAGE TO PROTEINS BY PEROXIDIZED LIPIDS. J Lipid Res. 1963 Apr;4:204–207. [PubMed] [Google Scholar]
  13. ELLMAN G. L., COURTNEY K. D., ANDRES V., Jr, FEATHER-STONE R. M. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961 Jul;7:88–95. doi: 10.1016/0006-2952(61)90145-9. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. GOLBERG L., MARTIN L. E., BATCHELOR A. Biochemical changes in the tissues of animals injected with iron. 3. Lipid peroxidation. Biochem J. 1962 May;83:291–298. doi: 10.1042/bj0830291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. HARRIS I. M., PRANKERD T. A., WESTERMAN M. P. Abnormality of phospholipids in red cells of patients with paroxysmal nocturnal haemoglobinuria. Br Med J. 1957 Nov 30;2(5056):1276–1277. doi: 10.1136/bmj.2.5056.1276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. HARTMANN R. C., JENKINS D. E., Jr PAROXYSMAL NOCTURNAL HEMOGLOBINURIA: CURRENT CONCEPTS OF CERTAIN PATHOPHYSIOLOGIC FEATURES. Blood. 1965 May;25:850–865. [PubMed] [Google Scholar]
  18. HORWITT M. K., HARVEY C. C., DUNCAN G. D., WILSON W. C. Effects of limited tocopherol intake in man with relationships to erythrocyte hemolysis and lipid oxidations. Am J Clin Nutr. 1956 Jul-Aug;4(4):408–419. doi: 10.1093/ajcn/4.4.408. [DOI] [PubMed] [Google Scholar]
  19. HUNTER F. E., Jr, GEBICKI J. M., HOFFSTEN P. E., WEINSTEIN J., SCOTT A. Swelling and lysis of rat liver mitochondria induced by ferrous ions. J Biol Chem. 1963 Feb;238:828–835. [PubMed] [Google Scholar]
  20. HUNTER F. E., Jr, SCOTT A., HOFFSTEN P. E., GEBICKI J. M., WEINSTEIN J., SCHNEIDER A. STUDIES ON THE MECHANISM OF SWELLING, LYSIS, AND DISTINTEGRATION OF ISOLATED LIVER MITOCHONDRIA EXPOSED TO MIXTURES OF OXIDIZED AND REDUCED GLUTATHIONE. J Biol Chem. 1964 Feb;239:614–621. [PubMed] [Google Scholar]
  21. HUNTER F. E., Jr, SCOTT A., HOFFSTEN P. E., GUERRA F., WEINSTEIN J., SCHNEIDER A., SCHUTZ B., FINK J., FORD L., SMITH E. STUDIES ON THE MECHANISM OF ASCORBATE-INDUCED SWELLING AND LYSIS OF ISOLATED LIVER MITOCHANDRIA. J Biol Chem. 1964 Feb;239:604–613. [PubMed] [Google Scholar]
  22. JACOB H. S., INGBAR S. H., JANDL J. H. OXIDATIVE HEMOLYSIS AND ERYTHROCYTE METABOLISM IN HEREDITARY ACATALASIA. J Clin Invest. 1965 Jul;44:1187–1199. doi: 10.1172/JCI105225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. LEIBETSEDER F., AHRENS E. H., Jr The fatty-acid composition of red cells in paroxysmal nocturnal haemoglobinuria. Br J Haematol. 1959 Oct;5:356–364. doi: 10.1111/j.1365-2141.1959.tb04046.x. [DOI] [PubMed] [Google Scholar]
  24. LEWIS S. M., SZUR L., DACIE J. V. The pattern of erythrocyte destruction in haemolytic anaemia, as studied with radioactive chromium. Br J Haematol. 1960 Apr;6:122–139. doi: 10.1111/j.1365-2141.1960.tb06224.x. [DOI] [PubMed] [Google Scholar]
  25. LOWRY O. H., ROBERTS N. R., LEINER K. Y., WU M. L., FARR A. L. The quantitative histochemistry of brain. I. Chemical methods. J Biol Chem. 1954 Mar;207(1):1–17. [PubMed] [Google Scholar]
  26. Lewis S. M., Danon D., Marikovsky Y. Electron-microscope studies of the red cell in paroxysmal nocturnal haemoglobinuria. Br J Haematol. 1965 Nov;11(6):689–695. doi: 10.1111/j.1365-2141.1965.tb00118.x. [DOI] [PubMed] [Google Scholar]
  27. MARTINEK R. G. METHOD FOR THE DETERMINATION OF VITAMIN E (TOTAL TOCOPHEROLS) IN SERUM. Clin Chem. 1964 Dec;10:1078–1086. [PubMed] [Google Scholar]
  28. MENGEL C. E., HYMAN B. N., O'MALLEY B. W., HOWELL D. A. COEXISTENT PAROXYSMAL NOCTURNAL AND COLD HEMOGLOBINURIA PRECEDED BY APLASTIC ANEMIA: A CASE REPORT AND FAMILY STUDY. Blood. 1964 Oct;24:451–457. [PubMed] [Google Scholar]
  29. MENGEL C. E., KANN H. E., Jr, HEYMAN A., METZ E. EFFECTS OF IN VIVO HYPEROXIA ON ERYTHROCYTES. II. HEMOLYSIS IN A HUMAN AFTER EXPOSURE TO OXYGEN UNDER HIGH PRESSURE. Blood. 1965 May;25:822–829. [PubMed] [Google Scholar]
  30. MENGEL C. E., KANN H. E., Jr, O'MALLEY B. W. INCREASED HEMOLYSIS AFTER INTRAMUSCULAR IRON ADMINISTRATION IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA. REPORT OF SIX OCCURRENCES IN FOUR PATIENTS, AND SPECULATIONS ON A POSSIBLE MECHANISM. Blood. 1965 Jul;26:74–81. [PubMed] [Google Scholar]
  31. MENGEL C. E., KANN H. E., SMITH W. W., HORTON B. D. EFFECTS OF IN VIVO HYPEROXIA ON ERYTHROCYTES. 1. HEMOLYSIS IN MICE EXPOSED TO HYPERBARIC OXYGENATION. Proc Soc Exp Biol Med. 1964 Jun;116:259–261. doi: 10.3181/00379727-116-29218. [DOI] [PubMed] [Google Scholar]
  32. MUNN J. I., CROSBY W. H. Paroxysmal nocturnal hemoglobinuria: evidence of defect of red cell stroma manifested by abnormalities of lipids. Proc Soc Exp Biol Med. 1957 Nov;96(2):480–482. doi: 10.3181/00379727-96-23513. [DOI] [PubMed] [Google Scholar]
  33. Mengel C. E., Kann H. E., Jr Effects of in vivo hyperoxia on erythrocytes. 3. In vivo peroxidation of erythrocyte lipid. J Clin Invest. 1966 Jul;45(7):1150–1158. doi: 10.1172/JCI105421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. O'Malley B. W., Mengel C. E., Meriwether W. D., Zirkle L. G., Jr Inhibition of erythrocyte acetylcholinesterase by peroxides. Biochemistry. 1966 Jan;5(1):40–44. doi: 10.1021/bi00865a006. [DOI] [PubMed] [Google Scholar]
  35. PHILLIPS G. B., ROOME N. S. Quantitative chromatographic analysis of the phospholipids of abnormal human red blood cells. Proc Soc Exp Biol Med. 1962 Feb;109:360–364. doi: 10.3181/00379727-109-27203. [DOI] [PubMed] [Google Scholar]
  36. Rosse W. F., Dacie J. V. Immune lysis of normal human and paroxysmal nocturnal hemoglobinuria (PNH) red blood cells. II. The role of complement components in the increased sensitivity of PNH red cells to immune lysis. J Clin Invest. 1966 May;45(5):749–757. doi: 10.1172/JCI105389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. TOLLERZ G., LANNEK N. PROTECTION AGAINST IRON TOXICITY IN VITAMIN E-DEFICIENT PIGLETS AND MICE BY VITAMIN E AND SYNTHETIC ANTIOXIDANTS. Nature. 1964 Feb 22;201:846–847. doi: 10.1038/201846a0. [DOI] [PubMed] [Google Scholar]
  38. TOWNES P. L., LOVELL G. R. Hereditary methemoglobinemia: a new variant exhibiting dominant inheritance of methemoglobin A. Blood. 1961 Jul;18:18–33. [PubMed] [Google Scholar]
  39. YACHNIN S., RUTHENBERG J. M. THE INITIATION AND ENHANCEMENT OF HUMAN RED CELL LYSIS BY ACTIVATORS OF THE FIRST COMPONENT OF COMPLEMENT AND BY FIRST COMPONENT ESTERASE; STUDIES USING NORMAL RED CELLS AND RED CELLS FROM PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA. J Clin Invest. 1965 Apr;44:518–534. doi: 10.1172/JCI105165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. ZINKHAM W. H., LENHARD R. E., Jr, CHILDS B. A deficiency of glucose-6-phosphate dehydrogenase activity in erythrocytes from patients with favism. Bull Johns Hopkins Hosp. 1958 Apr;102(4):169–175. [PubMed] [Google Scholar]
  41. ZIRKLE L. G., Jr, MENGEL C. E., BUTLER S. A., FUSON R. EFFECTS OF IN VIVO HYPEROXIA ON ERYTHROCYTES. IV. STUDIES IN DOGS EXPOSED TO HYPERBARIC OXYGENATION. Proc Soc Exp Biol Med. 1965 Jul;119:833–837. doi: 10.3181/00379727-119-30314. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES