Skip to main content
SpringerLink
Log in

Role of Hemoglobin Denaturation and Band 3 Clustering in Initiating Red Cell Removal

  • Chapter
Red Blood Cell Aging

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 307))

Abstract

While multiple mechanisms likely exist to assure that a defective erythrocyte does not escape removal by macrophages, we believe that the more heavily used clearance pathways will have certain characteristics in common. First, the pathway should involve a change in components already present in the circulating erythrocytes, since de novo protein synthesis will have terminated before the erythrocyte reaches maturity. Second, the changes initiating the removal sequence must eventually be manifested on the exofacial surface of the cell, since a macrophage has little means of detecting an intracellular biochemical lesion. And finally, the exofacial changes recognized by the macrophage must be inducible by a change in the biochemistry of the cytoplasm, since cells that develop intracellular defects early in their lifespans are also removed early (e.g., sickle cells, (1) ß-thalassemic cells, (2) cells with enzyme deficiencies, (3) cells treated with oxidants, (4) etc). That is, a linkage of some sort must exist between the functional state of components in the cytoplasm and markers at the cell surface recognized by macrophages. The hypothesis outlined below describes how hemoglobin, the most abundant protein in the cytoplasm, and band 3, the most prominent protein in the membrane cooperate to establish this linkage, transducing information regarding the biochemical integrity of the cell to the reticuloendothelial system which is responsible for aged/abnormal cell clearance.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. P. R. McCurdy and A. S. Sherman, Irreversibly sickled cells and red cell survival in sickle cell anemia, Amer. J. Med. 64:253 (1978).

    Article  PubMed  CAS  Google Scholar 

  2. E. A. Rachmilewitz, E. Shinar, O. Shalev, U. Galili and S. L. Schrier, Erythrocyte membrane alterations in ß-thalassemia, Clinics in Haematology 14:163 (1985).

    PubMed  CAS  Google Scholar 

  3. J. J. Kaneko, Comparative erythrocyte metabolism, Adv. Vet. Sci. Comp. Med. 18:117 (1974).

    PubMed  CAS  Google Scholar 

  4. D. A. Bates and C. C. Winterbourn, Hemoglobin denaturation, lipid peroxidation and hemolysis in phenylhydrazine-induced anemia, Biochim. Biophys. Acta 798:84 (1984).

    Article  PubMed  CAS  Google Scholar 

  5. S. Horn, J. Copas and N. Bashan, A lectin-like receptor on murine macrophage is involved in the recognition and phagocytosis of human red cells oxidized by Phenylhydrazine, Biochem. Pharm. 39:775 (1990).

    Article  PubMed  CAS  Google Scholar 

  6. M. Beppu, M. Ochiai and K. Kikugawa, Macrophage recognition of periodate-treated erythrocytes: involvement of disulfide formation of the erythrocyte membrane proteins, Biochim. Biophys. Acta 979:35 (1989).

    Article  PubMed  CAS  Google Scholar 

  7. P. S. Low, Interaction of native and denatured hemoglobins with band 3: consequences for erythrocytes structure and function, in “Red Blood Cell Membranes” P. Agre and J. C. Parker, ed., Marcel Dekker, Inc. NY, p. 237 (1989).

    Google Scholar 

  8. P. S. Low and R. Kannan, Effect of hemoglobin denaturation on membrane strucutre and IgG binding: role in red cell aging, in “The Red Cell: Seventh Ann Arbor Conference”, Alan R. Liss, Inc. p. 525 (1989).

    Google Scholar 

  9. S. M. Waugh, B. M. Willardson, R. Kannan, R. J. Labotka and P. S. Low, Heinz bodies induce clustering of band 3, glycophorin, and ankyrin in sickle cell erythrocytes, J. Clin. Invest. 78:1155 (1986).

    Article  PubMed  CAS  Google Scholar 

  10. P. S. Low, S. M. Waugh, K. Zinke and D. Drenckhahn, The role of hemoglobin denaturation and band 3 clustering in red blood cell aging, Science 227:531 (1985).

    Article  PubMed  CAS  Google Scholar 

  11. H. Muller and H. U. Lutz, Binding of autologous IgG to human red blood cells before and after ATP-depletion, Biochim. Biophys. Acta 729:249 (1983).

    Article  PubMed  CAS  Google Scholar 

  12. P. Hochstein and S. K. Jain, Association of lipid peroxidation and polymerization of membrane proteins with erythrocyte aging, FASEB 40:183 (1981).

    CAS  Google Scholar 

  13. A. Elgsaeter, D. M. Shotton and D. Branton, Intermembrane particle aggregation in erythrocyte ghosts, Biochim. Biophys. Acta 426:101 (1976).

    Article  PubMed  CAS  Google Scholar 

  14. F. Turrini, A. Naitana, L. Mannuzzu, G. P. Pescarmona and P. Arese, Increased red cell calcium, decreased calcium adenosine triphosphatase, and altered membrane proteins during Fava bean hemolysis in glucose-6-phosphate dehydrogenase-deficient (Mediterranean variant) individuals, Blood 66:302 (1985).

    PubMed  CAS  Google Scholar 

  15. M. R. Clark, Senescence of red blood cells: progress and problems, Physiol. Rev. 68:503 (1988).

    PubMed  CAS  Google Scholar 

  16. J. R. Barber and S. Clarke, Membrane protein carboxyl methylation increase with human erythrocyte age, J. Biol. Chem. 258:1189 (1983).

    PubMed  CAS  Google Scholar 

  17. K. Yamamoto, M. Yamada and Y. Kato, Age-related and phenylhydrazine-induced activation of the membrane-associated cathepsin E in human erythrocytes, J. Biochem. 105:114 (1989).

    PubMed  CAS  Google Scholar 

  18. M. M. B. Kay, K. Sorensen, P. Wong and P. Bolton, Antigenicity, storage and aging: physiologic autoantibodies to cell membrane and serum proteins and the senescent cell antigen, Molec. and Cell. Biochem. 49:65 (1982).

    CAS  Google Scholar 

  19. H. Vlassara, J. Valinsky, M. Brownlee, C. Cerami, S. Nishimoto and A. Cerami, Advanced glycolysation endproducts on erythrocyte cell surface induce receptor-mediated phagocytosis by macrophages. A model for turnover of aging cells, J. Exp. Med. 166:539 (1987).

    Article  PubMed  CAS  Google Scholar 

  20. K. Miyahara and M. J. Spiro, Nonuniform loss of membrane glycoconjugates during in vivo aging of human erythrocytes: studies of normal and diabetic red cell saccharides, Arch. Biochem. Biophys. 232:310 (1984).

    Article  PubMed  CAS  Google Scholar 

  21. M. A. Zago, D. T. Covas, M. S. Figueiredo, C. Bottura, Red cell pits appear preferentially in old cells after splenectomy, Acta Haemat. 76:54 (1986).

    Article  PubMed  CAS  Google Scholar 

  22. A. Fazi, E. Piatti, A. Accorsi and M. Magnani, Cell age dependent decay of human erythrocytes glucose-6-phosphate isomerase, Biochim. Biophys. Acta 998:286 (1989).

    Article  PubMed  CAS  Google Scholar 

  23. C. Seaman, S. Wyss and S. Piomelli, The decline in energetic metabolism with aging of the erythrocyte and its relationship to cell death, Amer. J. Hemat. 8:31 (1980).

    Article  CAS  Google Scholar 

  24. H. Q. Campwala and J. F. Desforges, Membrane-bound hemichrome in density-separated cohorts of normal (AA) and sickled (SS) cells, J. Lab. Clin. Med. 99:25 (1982).

    PubMed  CAS  Google Scholar 

  25. D. A. Sears, J. M. Friedman and D. R. White, Binding of intracellular protein to the erythrocyte membrane during incubation: the production of Heinz bodies, J. Lab. Clin. Med. 86:722 (1975).

    PubMed  CAS  Google Scholar 

  26. J. G. Selwyn, Heinz bodies in red cells after splenectomy and phenacetin administration, Brit. J. Haematol. 4:173 (1955).

    Article  Google Scholar 

  27. T. J. Mueller, C. W. Jackson, M. E. Dockter and M. Morrison, Membrane skeletal alterations during in vivo mouse red cell aging: increase in the band 4.1a:4.1b ratio, J. Clin. Invest. 79:492 (1987).

    Article  PubMed  CAS  Google Scholar 

  28. T. Suzuki and G. Dale, membrane proteins in senescent erythrocytes, Biochem. J. 257:37 (1989).

    PubMed  CAS  Google Scholar 

  29. S. K. Jain, Evidence for membrane lipid peroxidation during the in vivo aging of human erythrocytes, Biochim. Biophys. Acta 937:205 (1988).

    Article  PubMed  CAS  Google Scholar 

  30. A. Brovelli, C. Seppi and C. Balduini, Modification of membrane protein organization during in vitro aging of human erythrocytes, Int. J. Biochem. 16:1115 (1984).

    Article  PubMed  CAS  Google Scholar 

  31. S. P. Sutera, R. A. Gardner, C. W. Boylan, G. L. Carroll, K. C. Chang, J. S. Marvel, C. Kilo, B. Gonen and J. R. Williamson, Age-related changes in deformability of human erythrocytes, Blood 65:275 (1985).

    PubMed  CAS  Google Scholar 

  32. J. M. Rifkind, K. Araki and E. C. Hadley, The relationship between the osmotic fragility of human erythrocytes and cell age, Arch. Biochem. Biophys. 222:582 (1983).

    Article  PubMed  CAS  Google Scholar 

  33. D. Aminoff, M. A. Ghalambor and C.J. Henrich, GOST, galactose oxidase and sialyl transferase, substrate and receptor sites in erythrocyte senescence, in “Erythrocyte Membranes 2. Recent Clinical and Experimental Advances”, W. C. Kruckerberg, J. W. Eaton and G. J. Brewer, ed., Liss: New York, p. 269 (1981).

    Google Scholar 

  34. U. Galili, I. Flechner, A. Knyszynski, D. Danon and E.A. Rachmilewitz, The natural anti-±-galactosyl IgG on human normal senescent red blood cells, Br. J. Haematol. 62:317 (1986).

    Article  PubMed  CAS  Google Scholar 

  35. T. Shiga, M. Sekiya, N. Maeda, K. Kon and M. Okazaki, Cell age-dependent changes in deformability and calcium accumulation of human erythrocytes, Biochim. Biophys. Acta 814:289 (1985).

    Article  PubMed  CAS  Google Scholar 

  36. S. M. Waugh and P. S. Low, Hemichrome binding to band 3: nucleation of Heinz bodies on the erythrocyte membrane, Biochemistry 24:34 (1985).

    Article  PubMed  CAS  Google Scholar 

  37. S. M. Waugh, J. A. Walder and P. S. Low, Partial characterization of the copolymerization reaction of erythrocyte membrane band 3 with hemichromes, Biochemistry 26:1777 (1987).

    Article  PubMed  CAS  Google Scholar 

  38. P. P. DaSilva, Translational mobility of the membrane intercalated particles of human erythrocyte ghosts, J. Cell. Biol. 53:777 (1972).

    Article  Google Scholar 

  39. K. Schlüter and D. Drenckhahn, Co-clustering of denatured hemoglobin with band 3: its role in binding of autoantibodies against band 3 to abnormal and aged erythrocytes, Proc. Natl. Acad. Sci.USA 83:6137 (1986).

    Article  PubMed  Google Scholar 

  40. F. Turrini, P. Arese, J. Yuan and P. S. Low, Clustering of integral membrane proteins of the human erythrocyte membrane stimulates autologous IgG binding, complement deposition and phagocytosis, submitted for publication (1991).

    Google Scholar 

  41. R. Kannan, R. Labotka and P. S. Low, Isolation and characterization of the hemichrome-stabilized membrane protein aggregates from sickle erythrocytes, J. biol. Chem. 263:13766 (1988).

    PubMed  CAS  Google Scholar 

  42. R. Kannan, Mechanism of aging of human red cells, Ph. D. Dissertation, Purdue University, 71 (1990).

    Google Scholar 

  43. R. Kannan, J. Yuan and P. S. Low, Isolation and characterization of antibody-enriched complexes from membranes of density fractionated human erythrocytes, manuscript submitted (1991).

    Google Scholar 

  44. M. Morrison, C. W. Jackson, T. J. Mueller, T. Huang, M. E. Dockter, W. S. Walker, J. A. Singer and H. H. Edwards, Does cell density correlate with red cell age?, Biomed. Biochim. Acta 42:S107 (1983).

    PubMed  CAS  Google Scholar 

  45. M. J. Clague and R. J. Cherry, A comparative study of band 3 aggregation in erythrocyte membranes by melittin and other cationic agents, Biochim. Biophys. Acta 980:93 (1989).

    Article  PubMed  CAS  Google Scholar 

  46. S. W. Hui, C. M. Stewart and R.J. Cherry, Electron microscopic observation of the aggregation of membrane proteins in human erythrocyte by mellitin, Biochim. Biophys. Acta 1023:335 (1990).

    Article  PubMed  CAS  Google Scholar 

  47. G. Lelkes, G. Lelkes, K. S. Merse and S. R. Hollan, Intense, reversible aggregation of intramembrane particles in non-haemolyzed human erythrocytes, Biochim. Biophys. Acta 732:48 (1983).

    Article  PubMed  CAS  Google Scholar 

  48. M. TenBrinke and J. DeReget, Cr-half time of heavy and light human erythrocytes, Scand. J. Haematol. 7:336 (1970).

    Article  CAS  Google Scholar 

  49. H. U. Lutz, A naturally occurring autoantibody to band 3 protein of human red blood cells and its possible role in removal of senescent red cells, in “Red Cell Membrane Glycoconjugates and Related Genetic Markers”, J-P Cartron, P. Rouger and C. Salmon, eds., p. 273 (1983).

    Google Scholar 

  50. M. Beppu, A. Mizukami, M. Nagoya and K. Kikugawa, Binding of anti-band 3 autoantibody to oxidatively damaged erythrocytes, J. Biol. Chem. 265:3226 (1990).

    PubMed  CAS  Google Scholar 

  51. M. M. B. Kay, Localization of senescent cell antigen on band 3, Proc. Natl. Acad. Sci. USA 81:5753 (1984).

    Article  PubMed  CAS  Google Scholar 

  52. A. G. Ehlenberger and V. Nussenzweig, The role of membrane receptors for C3b and C3d in phagocytosis, J. Exp. Med. 145:357 (1977).

    Article  PubMed  CAS  Google Scholar 

  53. H. U. Lutz, F. Bussolino, R. Flepp, S. Fasler, P. Stammler, M. D. Kazatchkine and P. Arese, Naturally occurring anti-band 3 antibodies and complement together mediate phagocytosis of oxidatively stressed human erythrocytes, Proc. Natl. Acad. Sci. USA 84:7368 (1987).

    Article  PubMed  CAS  Google Scholar 

  54. N. Yousaf, J. C. Howard and B. D. Williams, Studies in the rat of antibody-sensitized and N-ethylmaleimide-treated erythrocyte clearance by the liver: effects of immune complex infusion and complement activation, Immunolgy 64:193 (1988).

    CAS  Google Scholar 

  55. A. Hermanowski-Vosatka, P. A. Detmers, O. Götze, S. C. Silverstein and S. D. Wright, Clustering of ligand on the surface of a particle enhances adhesion to receptor-bearing cells, J. Biol. Chem. 263:17822 (1988).

    PubMed  CAS  Google Scholar 

  56. M. M. B. Kay, Role of physiologic autoantibody in the removal of senescent human red cells, J. Supramol. Struct. 9:555 (1978).

    Article  PubMed  CAS  Google Scholar 

  57. G. M. Shaw, D. Aminoff, S. P. Balcerzak and A. F. LoBuglio, Clustered IgG on human red blood cell membranes may promote human lymphocyte antibody-dependent cell-mediated cytotoxicity, J. Immunol. 125:501 (1980).

    PubMed  CAS  Google Scholar 

  58. R. A. Rifkind, Heinz body anemia: an ultrastructural study. II. Red cell sequestration and destruction, Blood 26:433 (1965).

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry, Purdue University, West Lafayette, Indiana, USA

    Philip S. Low

Authors
  1. Philip S. Low
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Urbino, Urbino, Italy

    Mauro Magnani

  2. University of Genoa, Genoa, Italy

    Antonio De Flora

Rights and permissions

Reprints and permissions

Copyright information

© 1991 Plenum Press, New York

About this chapter

Cite this chapter

Low, P.S. (1991). Role of Hemoglobin Denaturation and Band 3 Clustering in Initiating Red Cell Removal. In: Magnani, M., De Flora, A. (eds) Red Blood Cell Aging. Advances in Experimental Medicine and Biology, vol 307. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5985-2_16

Download citation

  • DOI: https://doi.org/10.1007/978-1-4684-5985-2_16

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-5987-6

  • Online ISBN: 978-1-4684-5985-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation