Membrane phospholipid asymmetry as a determinant of erythrocyte recognition by macrophages (original) (raw)

Abstract

To assess the role of transbilayer phospholipid distribution in the recognition and phagocytosis of erythrocytes by macrophages, human erythrocytes with either a symmetric or asymmetric distribution of membrane phospholipids were prepared by hypotonic hemolysis and then incubated with cultures of human monocyte-derived macrophages. Erythrocytes with an abnormal, symmetric distribution were phagocytosed 4 times more readily than their counterparts with an asymmetric distribution or than normal, asymmetric intact erythrocytes. This enhanced phagocytosis correlated with two biophysical properties of the membrane: the spacing of phospholipids, as assessed by binding of the dye merocyanine 540, and the relative hydrophobicity, as measured by aqueous two-phase polymer partitioning. These results suggest a mechanism by which loss of membrane asymmetry is translated into recognition by macrophages and provide guidelines in loading erythrocytes that may be useful in manipulating the mode of delivery when erythrocytes are used as drug carriers in vivo.

3311

Images in this article

Selected References

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

  1. Bennett G. D., Kay M. M. Homeostatic removal of senescent murine erythrocytes by splenic macrophages. Exp Hematol. 1981 Mar;9(3):297–307. [PubMed] [Google Scholar]
  2. Choe H. R., Williamson P., Rubin E., Schlegel R. A. Disruption of phospholipid asymmetry in erythrocyte vesicles deficient in spectrin. Cell Biol Int Rep. 1985 Jul;9(7):597–606. doi: 10.1016/0309-1651(85)90051-7. [DOI] [PubMed] [Google Scholar]
  3. Del Buono B. J., Williamson P. L., Schlegel R. A. Alterations in plasma membrane lipid organization during lymphocyte differentiation. J Cell Physiol. 1986 Mar;126(3):379–388. doi: 10.1002/jcp.1041260308. [DOI] [PubMed] [Google Scholar]
  4. Hebbel R. P., Yamada O., Moldow C. F., Jacob H. S., White J. G., Eaton J. W. Abnormal adherence of sickle erythrocytes to cultured vascular endothelium: possible mechanism for microvascular occlusion in sickle cell disease. J Clin Invest. 1980 Jan;65(1):154–160. doi: 10.1172/JCI109646. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Ihler G. M. Erythrocyte carriers. Pharmacol Ther. 1983;20(2):151–169. doi: 10.1016/0163-7258(83)90037-2. [DOI] [PubMed] [Google Scholar]
  6. Kruse C. A., Tin G. W., Baldeschwieler J. D. Stability of erythrocyte ghosts: a gamma-ray perturbed angular correlation study. Proc Natl Acad Sci U S A. 1983 Mar;80(5):1212–1216. doi: 10.1073/pnas.80.5.1212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Lubin B., Chiu D., Bastacky J., Roelofsen B., Van Deenen L. L. Abnormalities in membrane phospholipid organization in sickled erythrocytes. J Clin Invest. 1981 Jun;67(6):1643–1649. doi: 10.1172/JCI110200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Musson R. A., Shafran H., Henson P. M. Intracellular levels and stimulated release of lysosomal enzymes from human peripheral blood monocytes and monocyte-derived macrophages. J Reticuloendothel Soc. 1980 Sep;28(3):249–264. [PubMed] [Google Scholar]
  9. Op den Kamp J. A. Lipid asymmetry in membranes. Annu Rev Biochem. 1979;48:47–71. doi: 10.1146/annurev.bi.48.070179.000403. [DOI] [PubMed] [Google Scholar]
  10. Reitherman R., Flanagan S. D., Barondes S. H. Electromotive phenomena in partition of erythrocytes in aqueous polymer two phase systems. Biochim Biophys Acta. 1973 Feb 28;297(2):193–202. doi: 10.1016/0304-4165(73)90065-2. [DOI] [PubMed] [Google Scholar]
  11. Schlegel R. A., McEvoy L., Williamson P. Membrane phospholipid asymmetry and the adherence of loaded red blood cells. Bibl Haematol. 1985;(51):150–156. doi: 10.1159/000410238. [DOI] [PubMed] [Google Scholar]
  12. Schlegel R. A., Phelps B. M., Cofer G. P., Williamson P. Enucleation eliminates a differentiation-specific surface marker from normal and leukemic murine erythroid cells. Exp Cell Res. 1982 Jun;139(2):321–328. doi: 10.1016/0014-4827(82)90256-7. [DOI] [PubMed] [Google Scholar]
  13. Schlegel R. A., Phelps B. M., Waggoner A., Terada L., Williamson P. Binding of merocyanine 540 to normal and leukemic erythroid cells. Cell. 1980 Jun;20(2):321–328. doi: 10.1016/0092-8674(80)90618-2. [DOI] [PubMed] [Google Scholar]
  14. Schlegel R., Tralka T. S., Willingham M. C., Pastan I. Inhibition of VSV binding and infectivity by phosphatidylserine: is phosphatidylserine a VSV-binding site? Cell. 1983 Feb;32(2):639–646. doi: 10.1016/0092-8674(83)90483-x. [DOI] [PubMed] [Google Scholar]
  15. Shukla S. D., Hanahan D. J. Membrane alterations in cellular aging: susceptibility of phospholipids in density (age)-separated human erythrocytes to phospholipase A2. Arch Biochem Biophys. 1982 Mar;214(1):335–341. doi: 10.1016/0003-9861(82)90038-8. [DOI] [PubMed] [Google Scholar]
  16. Skutelsky E., Danon D. Reduction in surface charge as an explanation of the recognition by macrophages of nuclei expelled from normoblasts. J Cell Biol. 1969 Oct;43(1):8–15. doi: 10.1083/jcb.43.1.8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Tanaka K. I., Ohnishi S. Heterogeneity in the fluidity of intact erythrocyte membrane and its homogenization upon hemolysis. Biochim Biophys Acta. 1976 Mar 5;426(2):218–231. doi: 10.1016/0005-2736(76)90333-3. [DOI] [PubMed] [Google Scholar]
  18. Tanaka Y., Schroit A. J. Insertion of fluorescent phosphatidylserine into the plasma membrane of red blood cells. Recognition by autologous macrophages. J Biol Chem. 1983 Sep 25;258(18):11335–11343. [PubMed] [Google Scholar]
  19. Walter H., Krob E. J., Brooks D. E. Membrane surface properties other than charge involved in cell separation by partition in polymer, aqueous two-phase systems. Biochemistry. 1976 Jul 13;15(14):2959–2964. doi: 10.1021/bi00659a004. [DOI] [PubMed] [Google Scholar]
  20. Williams J. H., Kuchmak M., Witter R. F. Fatty acids in phospholipids isolated from human red cells. Lipids. 1966 Nov;1(6):391–398. doi: 10.1007/BF02532542. [DOI] [PubMed] [Google Scholar]
  21. Williamson P., Algarin L., Bateman J., Choe H. R., Schlegel R. A. Phospholipid asymmetry in human erythrocyte ghosts. J Cell Physiol. 1985 May;123(2):209–214. doi: 10.1002/jcp.1041230209. [DOI] [PubMed] [Google Scholar]
  22. Williamson P., Bateman J., Kozarsky K., Mattocks K., Hermanowicz N., Choe H. R., Schlegel R. A. Involvement of spectrin in the maintenance of phase-state asymmetry in the erythrocyte membrane. Cell. 1982 Oct;30(3):725–733. doi: 10.1016/0092-8674(82)90277-x. [DOI] [PubMed] [Google Scholar]
  23. Williamson P., Mattocks K., Schlegel R. A. Merocyanine 540, a fluorescent probe sensitive to lipid packing. Biochim Biophys Acta. 1983 Jul 27;732(2):387–393. doi: 10.1016/0005-2736(83)90055-x. [DOI] [PubMed] [Google Scholar]
  24. Zaslavsky B. Y., Miheeva L. M., Rogozhin S. V. Possibility of analytical application of the partition in aqueous biphasic polymeric systems technique. Biochim Biophys Acta. 1978 Jun 16;510(1):160–167. doi: 10.1016/0005-2736(78)90137-2. [DOI] [PubMed] [Google Scholar]
  25. van Oss C. J. Phagocytosis as a surface phenomenon. Annu Rev Microbiol. 1978;32:19–39. doi: 10.1146/annurev.mi.32.100178.000315. [DOI] [PubMed] [Google Scholar]