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Plasma Factor Triggering Alternative Complement Pathway Activation by Liposomes

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Abstract

Several plasma components, such as complement (C) components, play a role in the clearance of liposomes from the circulation. The interactions between liposomes and the C system were investigated in this study. Multilamellar vesicle (MLV) liposomes, which were damaged by activation of the complement, became susceptible depending on the density of cetylmannoside (Man) on the liposome membrane, and activation proceeded through the alternative C pathway as observed for liposomes without Man (PC-MLV) (K. Funato et al, Biochim. Biophys. Acta 1103:198–204, 1992). In addition, the capacity of Man-modified liposomes (Man-MLV) to activate the alternative C pathway was abolished by preadsorption of plasma with Man-MLV but not with PC-MLV. The results suggest that a specific plasma factor adsorbed with Man-MLV was responsible for the augmentation of the C activation and, further, that the rapid clearance of Man-MLV from the circulation is caused by both enhanced C-mediated liposome permeability and enhanced C-mediated phagocytosis of liposomes.

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REFERENCES

  1. M. Harish and P. D. Patel. Serum opsonins and liposomes: Their interaction and opsonophagocytosis. Crit. Rev. Ther. Drug Carrier Syst. 9:39–90 (1992).

    Google Scholar 

  2. R. L. Juliano and G. Lin. The interaction of plasma proteins with liposomes: Protein binding and effects on the clotting and complement system. In B. H. Tom and H. R. Six (eds.), Liposomes and Immunobiology, Elsevier Science, Amsterdam, 1980, pp. 49–66.

    Google Scholar 

  3. F. Bonte and R. L. Juliano. Interaction of liposomes with serum proteins. Chem. Phys. Lipids 40:359–372 (1986).

    Google Scholar 

  4. A. Chonn, S. C. Semple, and P. R. Cullis. Association of blood proteins with large unilamellar liposomes in vivo: Relation to circulation lifetimes. J. Biol. Chem. 267:18759–18765 (1990).

    Google Scholar 

  5. K. Funato, Y. Ritsuko, and H. Kiwada. Contribution of complement system on destabilization of liposomes composed of hydrogenated egg phosphatidylcholine in rat fresh plasma. Biochim. Biophys. Acta 1103:198–204 (1992).

    Google Scholar 

  6. H. Harashima, K. Sakata, K. Funato, and H. Kiwada. Enhanced hepatic uptake of liposomes through complement activation depending on the size of liposomes. Pharm. Res. 11:402–406 (1993).

    Google Scholar 

  7. P. K. Das, G. J. Murray, G. C. Zirzow, R. O. Brady, and J. A. Barranger. Lectin-specific targeting of β-glucocerebrosidase to different liver cells via glycosylated liposomes. Biochem. Med. 33:124–131 (1985).

    Google Scholar 

  8. P. Ghosh and B. K. Bachhawat. Grafting of different glycosides on the surface of liposomes and its effect on the tissue distribution of 125I-labelled γ-globulin encapsulated in liposomes. Biochim. Biophys. Acta 632:562–572 (1980).

    Google Scholar 

  9. C. D. Muller and F. Schuber. Neo-mannosylated liposomes: Synthesis and interaction with mouse Kupffer cells and resident perioneal macrophages. Biochim. Biophys. Acta 986:97–105 (1989).

    Google Scholar 

  10. G. Barratt, J.-P. Tenu, A. Yapo, and J.-F. Petit. Preparation and characterisation of liposomes containing mannosylated phospholipids capable of targetting drugs to macrophages. Biochem. Biophys. Acta 862:153–164 (1986).

    Google Scholar 

  11. C. Yamashita, H. Matsuo, K. Akiyama, and K. Kiwada. Enhancing effect of cetylmannoside on targeting of liposomes to kupffer cells in rats. Int. J. Pharm. 70:225–233 (1991).

    Google Scholar 

  12. H. Kiwada, H. Nimura, Y. Fujisaki, S. Yamada, and Y. Kato. Application of synthetic alkyl glycoside vesicles as drug carriers. I. Preparation and physical properties. Chem. Pharm. Bull. 33:753–759 (1985).

    Google Scholar 

  13. S. Tanaka, F. Kitamura, and T. Suzuki. Studies on the hemolytic activity of the classical and alternative pathway of complement in various animal species. Complement 4:33–41 (1987).

    Google Scholar 

  14. W. Miyazaki, H. Tamaoka, M. Shinohara, H. Kaise, T. Izawa, Y. Nakano, T. Kinoshita, K. Hong, and K. Inoue. A complement inhibitor produced by Stachybotrys complementi, nov. sp. K-76, a new species of fungi imperfecti. Microbiol. Immunol. 24:1091–1108 (1980).

    Google Scholar 

  15. D. P. Fine, S. R. Marney, D. G. Colley, Jr., J. S. Sergent, and R. M. D. Prez. C3 shunt activation in human serum chelated with EGTA. J. Immunol. 109:807–809 (1972).

    Google Scholar 

  16. C. Mold and H. Gewurz. Activation of human complement by liposomes: Serum factor requirement for alternative pathway activation. J. Immunol. 125:696–700 (1980).

    Google Scholar 

  17. I. Ihara, Y. Harada, S. Ihara, and M. Kawakami. A new complement-dependent bactericidal factor found in nonimmune mouse sera: Specific binding to polysaccharide of Ra chemotype salmonella. J. Immunol. 128:1256–1260 (1982).

    Google Scholar 

  18. J. E. Schweinle, R. A. B. Ezekowitz, A. J. Tenner, M. Kuhlman, and K. A. Joiner. Human mannose-binding protein activates the alternative complement pathway and enhances serum bactericidal activity on a mannose-rich isolate of salmonella. J. Clin. Invest. 84:1821–1829 (1989).

    Google Scholar 

  19. M. A. Wilson and T. R. Kozel. Contribution of antibody in normal human serum to early deposition of C3 onto encapsulated and nonencapsulated Cryptococcus neoformans. Infect. Immun. 60:754–761 (1992).

    Google Scholar 

  20. H. A. Schenkein and S. Ruddy. The role of immunoglobulins in alternative complement pathway activation by zymosan. J. Immunol. 126:7–10 (1981).

    Google Scholar 

  21. K. Ikeda, T. Sannoh, N. Kawasaki, T. Kawasaki, and I. Yamashina. Serum lectin with known structure activates complement through the classical pathway. J. Biol. Chem. 262:7451–7454 (1987).

    Google Scholar 

  22. Y.-H. Ji, M. Matsushita, H. Okada, T. Fujita, and M. Kawakami. The C4 and C2 but not C1 components of complement are responsible for the complement activation triggered by the Ra-reactive factor. J. Immunol. 141:4271–4275 (1988).

    Google Scholar 

  23. M. Ohta, M. Okada, I. Yamashina, and T. Kawasaki. The mechanism of carbohydrate-mediated complement activation by the serum mannan-binding protein. J. Biol. Chem. 265:1980–1984 (1990).

    Google Scholar 

  24. M. Matsushita, A. Takahashi, H. Hatsuse, M. Kawakami, and T. Fujita. Human mannose-binding protein is identical to a component of Ra-reactive factor. Biochem. Biophys. Res. Commun. 183:645–651 (1992).

    Google Scholar 

  25. S. Inai, K. Nagaki, S. Ebisu, K. Kato, S. Kotani, and A. Misaki. Activation of the alternative complement pathway by water-insoluble glucans of streptococcus mutans: The relation between their chemical structures and activating potencies. J. Immunol. 117:1256–1260 (1976).

    Google Scholar 

  26. R. L. Richards, H. Gewurz, J. Siegel, and C. R. Alving. Interactions of C-reactive protein and complement with liposomes. J. Immunol. 122:1185–1189 (1979).

    Google Scholar 

  27. C. R. Alving, R. L. Richards, and A. A. Guirguis. Cholesterol-dependent human complement activation resulting in damage to liposomal model membranes. J. Immunol. 118:342–347 (1977).

    Google Scholar 

  28. P. S. Seifert and M. D. Kazatchkine. Generation of complement anaphylatoxins and C5b-9 by crystalline cholesterol oxidation derivatives depends on hydroxyl group number and position. Mol. Immun. 24:1303–1308 (1987).

    Google Scholar 

  29. A. S. D. Pang, A. Katz, and J. O. Minta. C3 deposition in cholesterol-induced atherosclerosis in rabbits: A possible etiologic role for complement in atherogenesis. J. Immunol. 123:1117–1122 (1979).

    Google Scholar 

  30. C. R. Alving and G. M. Swartz, Jr. Antibodies to cholesterol, cholesterol conjugates, and liposomes: Implications for atherosclerosis and autoimmunity. Crit. Rev. Immunol. 10:441–453 (1991).

    Google Scholar 

  31. H. Kiwada, T. Miyajima, and Y, Kato. Studies on the uptake mechanism of liposomes by perfused rat liver. II. An indispensable factor for liver uptake in serum. Chem. Pharm. Bull. 35:1189–1195 (1987).

    Google Scholar 

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Funato, K., Yamashita, C., Kamada, J. et al. Plasma Factor Triggering Alternative Complement Pathway Activation by Liposomes. Pharm Res 11, 372–376 (1994). https://doi.org/10.1023/A:1018952718496

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