Lysophosphatidylcholine (Lysolecithin) and its Synthetic Analogues. Immunomodulating and Other Biologic Effects

  • P. G. Munder
  • M. Modolell
  • R. Andreesen
  • H. U. Weltzien
  • O. Westphal


Since the early work of Bergenhem and Fahraeus on the hemolytic activity of naturally occurring 2-lysophosphatidylcholine (lysolecithin) (LPC) [12] this substance has off and on been considered as a biologically active compound. It is present as a minor phospholipid in the plasma (8–12%) [23] and cellular membranes (≥ 3%) [21, 27, for review 79]. It is highly surface-active (44.3 dyn/cm) [4] and, therefore, potentially cytotoxic if incubated with cells in serum — or plasma free —media [4, 30, 31, 33, 44, 72, 76]. Addition in sublytic amounts, however, stimulates phagocytosis [16, 20, 80], changes the surface properties of erythrocytes [36], increases the Concanavalin-A (Con-A)-induced agglutination of erythrocytes [75], and may be used as a cell-fusing agent [58]. Furthermore, it has been claimed to be involved in hypersensitivity [38, 70] and inflammatory reactions [17].


Synthetic Analogue Peritoneal Cell Ehrlich Ascites Tumor Cell Primary Immune Response Antigenic Stimulus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Andreesen, R., Modolell, M., Weltzien, H. U., Eibl, H., Common, H. H., Löhr, G. W., Munder, P. G.: Selective destruction of human leukemic cells by alkyl-lysophospholipids. Cancer Res. 38, 3894 (1978)PubMedGoogle Scholar
  2. 2.
    Andreesen, R., Modolell, M., Munder, P. G.: Alkyl-lysophospholipids as new antimetabolites selective for human leukemic cells. Proceedings of the XII. Int. Cancer Congress, Buenos Aires, Vol. 3, p. 241, 1978Google Scholar
  3. 3.
    Arnold, B., Miller, J.F.A.P., Weltzien, H. U.: Lysolecithin analogs as adjuvants in delayed type hypersensitivity in mice. I. Characterization of the adjuvant effect. Eur. J. Immunol, (in press, 1979)Google Scholar
  4. 4.
    Arnold, D., Weltzien, H. U.: Über die strukturabhängige hämolytische Aktivität einiger Cholin-Phosphatide. Z. Naturforsch. [C] 23b, 675 (1968)Google Scholar
  5. 5.
    Arnold, B., Reuther, R., Weltzien, H. U.: Distribution and metabolism of synthetic alkyl-analogs of lysophosphatidylcholine in mice. Biochim. Biophys. Acta 530, 47 (1978)PubMedGoogle Scholar
  6. 6.
    Aunis, D., Pescheloche, M., Zwiller, J., Mandel, P.: Effect of lysolecithin on adenylate cyclase and guanylate Cyclase activities in bovine adrenal medullary plasma membranes. J. Neurochem. 31, 355 (1978)PubMedCrossRefGoogle Scholar
  7. 7.
    Barton, M. A., Diener, E.: A new perspective on B cell triggering: Control of the immune response by organizational changes in the lipid bilayer. Transplant. Rev. 23, 5 (1975)PubMedGoogle Scholar
  8. 8.
    Bausert, W.: Der Einfluß von synthetischen Lysolecithin-Analoga auf das Wachstum experimenteller Tumoren der Maus. Thesis, University of Freiburg i. Br. 1978Google Scholar
  9. 9.
    Berdel, W.: Metastasierung des 3-Lewis Lungenkarzinoms (3-LL) unter dem Einfluß von Lysophospholipiden und Lysophospholipidaktivierten Makrophagen. Thesis, University of Freiburg i. Br. 1979Google Scholar
  10. 10.
    Berdel, W., Bausert, W., Weltzien, H. U., Modolell, M., Munder, P. G.: Metastatic growth of 3-Lewis lung carcinoma treated with alkyl-lysophospholipids and lysophospholipid activated macrophages. J. Natl. Cancer Inst, (in press 1979)Google Scholar
  11. 11.
    Bell, D. P.: Lipoprotein lipid exchange in biological system. In: Low density lipoproteins, Day, C. E., Levy, R. S., ed., pp. 111–126. New York: Plenum Press 1976Google Scholar
  12. 12.
    Bergenhem, B., Fahraeus, R.: Über spontane Hämolysinbildung im Blut unter besonderer Berücksichtigung der Physiology der Milz. Z. Ges. Exp. Med. 97, 555 (1936)CrossRefGoogle Scholar
  13. 13.
    Betz, O. M.: Untersuchungen zur Immunmodulation durch Lysophospholipide. Thesis, University of Freiburg i. Br. 1979Google Scholar
  14. 14.
    Blattmann, R. B.: Untersuchungen in vitro zum Wirkungsmechanismus von Lysophosphatiden auf das Wachstum experimenteller Tumoren. Thesis, University of Freiburg i. Br. 1977Google Scholar
  15. 15.
    Brash, J. L., Lyman, D. J.: The adsorption of proteins and lipids to non-biological surfaces. In: The chemistry of biosurfaces. Hair, M. L., ed., pp. 177–232. New York: Marcell Dekker Inc. 1971Google Scholar
  16. 16.
    Burdzy, K., Munder, P. G., Fischer, H., Westphal, O.: Steigerung der Phagocytose von Peritonealmakrophagen durch Lysolecithin. Z. Naturforsch. [C] 19 b, 1118 (1964)Google Scholar
  17. 17.
    Cotran, R. S., Majno, G.: A light and electron microscopic analysis of vascular injury. Ann. N. Y. Acad. Sci. 116, 750 (1964)PubMedCrossRefGoogle Scholar
  18. 18.
    Dresser, D. W.: Adjuvanticity of vitamin A. Nature 217, 527 (1966)CrossRefGoogle Scholar
  19. 19.
    Dresser, D. W.: Effectiveness of lipid and lipidophilic substances as adjuvants. Nature 191, 1169 (1961)PubMedCrossRefGoogle Scholar
  20. 20.
    Elsbach, P., van den Berg, J. W. O., van den Bosch, H., van Deenen, L. L. M.: Metabolism of phospholipids by polymorphonuclear leukocytes. Biochim. Biophys. Acta 106, 338 (1965)PubMedGoogle Scholar
  21. 21.
    Ferber, E., Resch, K.: Structure and physiologic role of lipids in the lymphocyte membrane. In: The lymphocyte: Structure and function, Marchalonis, J., ed., pp. 593–620. New York: Marcell Dekker Inc. 1977Google Scholar
  22. 22.
    Fischer, H., Haupt, I.: Das cytolysierende Prinzip von Serumkomplement Z. Naturforsch. 16 b, 321 (1961)Google Scholar
  23. 23.
    Freudenberg, M. A.: Über den Einfluß von Lysolezithin und von synthetischen Lysolezithinanaloga auf die Stimulierung von Lymphozyten in Vitro. Thesis, Universität of Freiburg 1974Google Scholar
  24. 24.
    Gillett, M. P. T., Besterman, E. M. M.: Plasma concentrations of lysolecithin and other phospholipids in the healthy population and in men suffering from atherosclerotic diseases. Atherosclerosis 22, 111 (1975)PubMedCrossRefGoogle Scholar
  25. 25.
    Goerke, J., de Gier, J., Bonsen, P. P. M.: Silica gel stimulates the hydrolysis of lecithin by phospholipase A. Biochim. Biophys. Acta 248, 245 (1971)PubMedGoogle Scholar
  26. 26.
    Haley, J. E., Stefano, G. B., Catapane, E. J.: Correlation between acidic phospholipids and serotonin and between lysolecithin and dopamine in ganglia of the marine mussel Mytilus edulis. Experientia 34, 210 (1977)CrossRefGoogle Scholar
  27. 27.
    Hill, E. E., Lands, W. E. M.: Phospholipid metabolism. In: ‘Lipid metabolism’; Wakil, S. J., ed., pp. 185–277. London, New York: Academic Press 1970Google Scholar
  28. 28.
    Joist, J. H., Dolezel, G., Cucuianu, M. P., Nishizawa, E. E., Mustard, J. F.: Inhibition and potentiations of platelet function by lysolecithin. Blood 49, 101 (1977)PubMedGoogle Scholar
  29. 29.
    Kirschbaum, R. B., Bosmann, H. B.: Lysolecithin enhancement of glycoprotein: glycosyltransferase activity. FEBS Lett. 34, 129 (1973)PubMedCrossRefGoogle Scholar
  30. 30.
    Klibansky, C., de Vries, A.: Quantitative study of erythrocyte-lysolecithin interaction. Biochim. Biophys. Acta 70, 176 (1963)PubMedCrossRefGoogle Scholar
  31. 31.
    Klibansky, C., Smorodinsky, I., de Vries, A.: Action of lysolecithin on normal and leukemic human leukocytes. Med. Pharmacol. Exp. 16, 297 (1967)Google Scholar
  32. 32.
    Lagrange, P. H., Mackaness, G. B., Miller, T. E.: Potentiation of T-cell-mediated immunity by selective suppression of antibody formation with cyclophosphamide. J. Exp. Med. 139, 1529 (1974)PubMedCrossRefGoogle Scholar
  33. 33.
    Langer, W.: Untersuchungen zum Wirkungsmechanismus immunologischer Adjuvantien. Thesis, University of Freiburg i. Br. 1973Google Scholar
  34. 34.
    Lebert, St.: Biochemische Untersuchungen zum Einfluß von SiO2-Modifikationen auf den Phospholipidstoffwechsel von Makrophagen. Thesis, University of Freiburg i. Br. 1975Google Scholar
  35. 35.
    Lyn, Y. N., Wassef, M. K., Horowitz, M. I.: Effect of aspirin and salicylic acid on phospholipid metabolizing enzymes. Fed. Proc. 37, 1832 (1978)Google Scholar
  36. 36.
    Marikovsky, Y., Brown, C. S., Weinstein, R. S., Wortis, H. H.: Effects of lysolecithin on the surface properties of human erythrocytes. Exp. Cell Res. 98, 313 (1976)PubMedCrossRefGoogle Scholar
  37. 37.
    Metcalf, D.: Hemopoietic colonies. Recent Results Cancer Res. 61, 1 (1977)Google Scholar
  38. 38.
    Middleton, E. Jr., Phillips, G. B.: Effect of lysolecithin on the smooth muscle stimulating activity of histamine, acetylcholine, 5-hydroxy-tryptamine, anaphylactic slow-reacting substance and brady-kinin. Nature 198, 758 (1963)PubMedCrossRefGoogle Scholar
  39. 39.
    Mitchison, N. A.: The immunogenic capacity of antigen taken up by peritoneal exudate cells. Immunology 16, 1 (1969)PubMedGoogle Scholar
  40. 40.
    Modolell, M., Andreesen, R., Pahlke, W., Brugger, U., Munder, P. G.: Disturbance of phospholipid metabolism during the selective destruction of tumor cells induced by alkyl-lysophospholipids. Cancer Res. (in press, 1979)Google Scholar
  41. 41.
    Modolell, M., Krause-Jauer, M., Munder, P. G.: Oxygen tension and pH as critical parameters for the cytotoxicity of macrophages. Proceedings of the XII. Int. Cancer Congress, Buenos Aires, Vol. 1, p. 163, 1978Google Scholar
  42. 42.
    Mookerja, S., Yung, J. W. M.: A study on the effect of lysolecithin and phospholipase A on membrane-bound galactosyltransferase. Can. J. Biochem. 52, 1053 (1974)CrossRefGoogle Scholar
  43. 43.
    Mookerja, S., Yung, J. W. M.: Stimulation of galactosyltransferase in liver microsome by lysolecithin. Biochem. Biophys. Res. Commun. 57, 815 (1974)CrossRefGoogle Scholar
  44. 44.
    Munder, P. G., Ferber, E., Fischer, H.: Lysophosphatide und Zellmembran. Untersuchungen über die Abhängigkeit der cytolytischen Wirkung des Lysolecithin von Membranenzymen. Z. Naturforsch. [C] 20 b, 1048 (1965)Google Scholar
  45. 45.
    Munder, P. G., Modolell, M., Ferber, E., Fischer, H.: Phospholipoide in quarzgeschädigten Makrophagen. Biochem. Z. 344, 310 (1966)PubMedGoogle Scholar
  46. 46.
    Munder, P. G., Modolell, M., Ferber, E., Fischer, H.: The relationship between macrophages and adjuvant activity. In: Mononuclear phagocytes, v. Furth, R., ed., pp. 445–460. Oxford: Blackwell Scientific Publications 1970Google Scholar
  47. 47.
    Munder, P. G., Modolell, M., Wallach, D. F. H.: Cell propagation on films of polymeric fluorocarbon as a means to regulate pericellular pH and pO2 in cultured monolayers. FEBS Lett. 15, 191 (1971)PubMedCrossRefGoogle Scholar
  48. 48.
    Munder, P. G., Modolell, M., Reatz, W., Luckenbach, G. A.: Primary antibody formation in vitro by mouse cells in a complete homologous system. Eur. J. Immunol. 3, 454 (1973)PubMedCrossRefGoogle Scholar
  49. 49.
    Munder, P. G., Modolell, M.: The influence of mycobacterium bovis and corynebacterium parvum on the phospholipid metabolism of macrophages. Recent Results Cancer Res. 47, 244 (1974)Google Scholar
  50. 50.
    Munder, P. G., Fischer, H., Weltzien, H. U., Oettgen, H. W., Westphal, O.: Lysolecithin analogs: a new class of immunopotentiators with antitumor activity. Proc. Am. Assoc. Cancer Res. 17, 174 (1976)Google Scholar
  51. 51.
    Munder, P. G., Weltzien, H. U., Modolell, M.: Lysolecithin analogs: a new class of immunopotentiators. In: Immunopathology, VIIth Int. Symposium, Miescher, P. A., ed., pp. 411–424. Basel: Schwabe and Co. 1976Google Scholar
  52. 52.
    Munder, P. G., Jansen, A., Andreesen, R., Modolell, M.: Synthetic lysophosphatides as inducers of macrophages cytotoxicity. Proceedings of the XII. Int. Cancer Congress, Buenos Aires, Vol. 1, p. 166, 1978Google Scholar
  53. 53.
    Nakano, K., Muramatsi, S.: Studies on the role of macrophages in the antibody response of mice: stimulation of T cell dependent antibody responses by tolerogenic soluble antigen trapped by macrophages. J. Reticuloenothel. Soc. 19, 347 (1976)Google Scholar
  54. 54.
    Old, L. J., Boyse, E. A., Clarke, D. A., Carswell, E.: Antigenic properties of chemically induced tumors. Ann. N. Y. Acad. Sci. 101, 80 (1962)CrossRefGoogle Scholar
  55. 55.
    O’Doherty, P. J. A., Smith, N. B., Kuksis, A.: Stimulation of CDP-choline biosynthesis by enantiomeric lysophosphatidylcholines in rat intestinal mucosa. Arch. Biochm. 180, 10 (1977)CrossRefGoogle Scholar
  56. 56.
    Perkins, E. H.: Digestion of antigen by peritoneal macrophages. In: Mononuclear phagocytes, v. Furth, R., ed., pp. 562–578. Oxford: Blackwell Scientific Publications 1970Google Scholar
  57. 57.
    Pernis, B., Paronetto, F.: Adjuvant effect of silica (trydimite) on antibody production. Proc. Soc. Exp. Biol. 110, 390 (1962)PubMedGoogle Scholar
  58. 58.
    Poole, A. R., Howell, J. I., Lucy, J. A.: Lysolecithin and cell fusion. Nature 227, 810 (1970)PubMedCrossRefGoogle Scholar
  59. 59.
    Portman, P. W., Alexander, M.: Influence of lysophosphatidylcholine on the metabolism of plasma lipoproteins. Biochim. Biophys. Acta 450, 322 (1976)PubMedGoogle Scholar
  60. 60.
    Rakhit, S.: On the structure of the renin inhibitor from hog kidney. Can. J. Biochem. 49, 1012 (1971)PubMedCrossRefGoogle Scholar
  61. 61.
    Rampone, A. J., Long, L. R.: The effect of phosphatidylcholine and lysophosphatidylcholine on the absorption and mucosal metabolism of oleic acid and cholesterol in vitro. Biochim. Biophys. Acta 486, 500 (1977)PubMedGoogle Scholar
  62. 62.
    Shier, W. T., Trotter, J. T. III.: Stimulation of liver microsomal sialyltransferase activity by lysolecithin. FEBS Lett. 62, 165 (1976)PubMedCrossRefGoogle Scholar
  63. 63.
    Shier, W. T., Baldwin, J. H., Nilsen-Hamilton, M., Hamilton, R. T., Thanassi, N. M.: Regulation of guanylate and adenylate cyclase activities by lysolecithin. Proc. Natl. Acad. Sci. U.S.A., 73, 1583 (1976)CrossRefGoogle Scholar
  64. 64.
    Shier, W. T.: Inhibition of prostaglandin synthesis by lysolecithin. Biochem. Biophys. Res. Commun. 78, 1168 (1977)PubMedCrossRefGoogle Scholar
  65. 65.
    Sjödahl, R., Tagesson, C.: Formation and inhibition of lysolecithin in human gallbladder bile. Acta Chir. Scand. 142, 395 (1976)PubMedGoogle Scholar
  66. 66.
    Snyder, F.: Ether-linked lipids and fatty alcohol precursors in neoplasma. In: Ether lipids, chemistry and biology, Snader, F., ed., pp. 273–296. New York: Academic Press 1972Google Scholar
  67. 67.
    Snyder, F., Malone, B., Piantadosi, C.: Tetrahydropteridine-dependent cleavage enzyme for O-alkyl-lipids: substrate specificity. Biochim. Biophys. Acta 316, 259 (1973)PubMedGoogle Scholar
  68. 68.
    Soodsma, J. F., Piantadosi, C., Snyder, F.: The biocleavage of alkyl-glyceryl ethers in Morris hepatomas and other transplantable neoplasms. Cancer Res. 30, 309 (1970)PubMedGoogle Scholar
  69. 69.
    Stein, Y., Stein, O.: Metabolism of labelled lysolecithin, lysophosphatidylethanolamin and lecithin in the rat. Biochim. Biophys. Acta 116, 95 (1966)PubMedGoogle Scholar
  70. 70.
    Strannegård, Ö., Roupe, G.: Adjuvant effect of lysolecithin analogues on the development of contact sensitivity in mice. Int. Arch. Allergy Appl. Immunol. 51, 198 (1976)PubMedCrossRefGoogle Scholar
  71. 71.
    Tagesson, C., Norrby, S., Sjödahl, R.: The prerequisites for local lysolecithin formation in the human gallbladder, II. Studies on the positional specificity of the phospholipase A activity. Scand. J. Gastroenterol. 13, 417 (1978)PubMedCrossRefGoogle Scholar
  72. 72.
    Tarnowski, G. S., Mountain, I. M., Stock, C. C., Munder, P. G. Weltzien, H. U., Westphal, O.: Effect of lysolecithin and analogs on mouse ascites tumors. Cancer Res. 38, 339 (1978)PubMedGoogle Scholar
  73. 73.
    Turcotte, J. G., Boyd, R. E., Quinn, J. G., Smeby, R. R.: Isolation and renin-inhibitory activity of phosphoglyceride from shark kidney. J. Med. Chem. 16, 166 (1973)PubMedCrossRefGoogle Scholar
  74. 74.
    Weltzien, H. U., Arnold, B., Westphal, O.: 14C-markierte Lysolecithin-Analoga. Liebigs Ann. Chem. p. 1439 (1973)Google Scholar
  75. 75.
    Weltzien, H. U.: Effects of lysolecithin and synthetic analogs on concanavalin A induced agglutination of chicken, human and bovine erythrocytes. Exp. Cell Res. 92, 111 (1975)PubMedCrossRefGoogle Scholar
  76. 76.
    Weltzien, H. U., Arnold, B., Reuther, G.: Quantiative studies on lysoleeithin-mediated hemolysis. Use of ether-deoxy lysolecithin analogs with varying aliphatic chain lengths. Biochim. Biophys. Acta 466, 411 (1977)PubMedCrossRefGoogle Scholar
  77. 77.
    Westphal, O., Westphal, U., Andreesen, R., Munder, P. G.: Anti-tumor effects of bacterial endotoxin (lipopolysaccharides, lipid A) and synthetic lysolecithin analogues. In: Proceedings of the study week on The role of nonspecific immunity in the prevention and treatment of cancer. (Vatican City, Oct. 17–21, 1977) Pontificia Academia Scientiarum: in press 1979Google Scholar
  78. 78.
    Westphal, O., Fischer, H., Munder, P. G.: Adjuvanticity of lysolecithin and synthetic analogues. 8th Int. Congress Biochemistry, Interlaken/Swiss, Abstract No. 129, Rochester: Staples Printers 1970Google Scholar
  79. 79.
    White, D. A.: The phospholipid composition of mammalian tissues. In: Form and function of phospholipids, Ansell, G. B., Hawthrne J. N., Dawson, R. M. C., eds., pp. 441–482. Amsterdam: Elsevier Scientific Publishing Company 1973Google Scholar
  80. 80.
    Wilkinson, P. J., Cater, D. B.: An electron-microscope study of the effects of lysolecithin on BP8 ascites-tumour cells and phagocytes of mice, compared with the effects of a specific anti-tumor serum plus complement. J. Pathol. 97, 219 (1969)PubMedCrossRefGoogle Scholar
  81. 81.
    Wood, R.: Tumor lipids: structural and metabolism studies of Ehrlich ascites cells. In: Tumor lipids, biochemistry and metabolism, Wood, R., ed., pp. 139–182. Champaign: American Oil Chemists Soc. Press 1973Google Scholar
  82. 82.
    Zwiller, J., Ciesielski-Treska, J., Mandel, P.: Effect of lysolecithin on guanylate and adenylate cyclase activities in neuroblastoma cells in culture. FEBS Lett. 69, 286 (1976)PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1980

Authors and Affiliations

  • P. G. Munder
    • 1
  • M. Modolell
    • 1
  • R. Andreesen
    • 1
  • H. U. Weltzien
    • 1
  • O. Westphal
    • 1
  1. 1.Max-Planck-Institut für ImmunbiologieFreiburgFederal Republic of Germany

Personalised recommendations