Abstract
Purpose. The effects of liposomes on nitric oxide (NO) production from mouse peritoneal macrophages following intraperitoneal injection of liposomes were investigated.
Methods. Mouse peritoneal macrophages were collected following intraperitoneal injection of liposomes and cultured with and without lipopolysaccharide (LPS). Peritoneal washing fluid was also collected from the mice injected with liposomes. NO production was evaluated by measuring the concentration of nitrite in the macrophage culture supernatant by Griess reagent.
Results. NO production stimulated by LPS was observed in peritoneal macrophages obtained from the liposome-treated mice, but liposomes did not activate macrophages directly to induce NO in response to LPS. NO production was higher in the liposomes composed of phospha-tidylcholine than that of negatively charged liposomes composed of phosphatidylserine. Peritoneal washing fluid obtained from mice injected with liposomes has a capacity to induce NO production in the macrophages from naive mice. This capacity was not diminished by heat-treatment at 100°C for 5 min.
Conclusions. Peritoneal macrophages were activated to produce NO in response to LPS following intraperitoneal injection of liposomes. They did not activate macrophages directly, and the induction of heat-stable macrophage priming factor, but not cytokines, is suggested.
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REFERENCES
S. Moncada, R. M. Palmer and E. A. Higgs. Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol. Rev. 43:109–142 (1991).
K. Aono, K. Isobe, I. Nakashima, S. Kondo, M. Miyachi and Y. Nimura. Kupffer cell cytotoxicity against hepatoma cells is related to nitric oxide. Biochem. Biophys. Res. Commun. 201:1175–1181 (1994).
R. Farias-Eisner, M. P. Sherman, E. Aeberhard and G. Chaudhuri. Nitric oxide is an important mediator for tumoricidal activity in vivo. Proc. Natl. Acad. Sce. USA. 91:9407–9411 (1994).
A. J. Schroitt and I. J. Fidler. Effects of liposomal structure and lipid composition on the activation of the tumoricidal properties of macrophages by liposomes containing muramyl dipeptide. Cancer Res. 42:161–167 (1982).
C. R. Alving. Liposomes as carrier of antigen and adjuvant. J. Immunol. Methods, 140:1–13 (1991).
D. J. Stuehr and C. F. Nathan. Nitric oxide: a macrophage product responsible for cytostasis and resparatory inhibition in tumor target cells. J. Exp. Med. 169:1543–1555 (1989).
G. R. Sambrano and D. Steinberg. Recognition of oxidatively damaged and apoptotic cells by an oxidized low density lipoprotein receptor on mouse peritoneal macrophages: Role of membrane phosphatidylserine. Proc. Natl. Acad. Sci. USA. 92:1396–1400 (1995).
C. F. Nathan and J. Hibbs. Role of nitric oxide synthesis in macrophage antimicrobial activity. Curr. Opin. Immunol. 3:65–70 (1991).
Y. Aramaki, F. Nitta, R. Matsuno, Y. Morimura and S. Tsuchiya. Inhibitory effects of negatively charged liposomes on nitric oxide production from macrophages stimulated by LPS. Biochem. Biophys. Res. Commun. 220:1–6 (1996).
Y. Aramaki, H. Suda and S. Tsuchiya. Interferon-γ inductive effect of liposomes as a immunoadjuvant. Vaccine 13:1809–1814 (1995).
A. J. H. Gearing, A. P. Johnstone and R. Thorpe. Production and assay of the interleukins. J. Immunol. Meth. 83:1–27 (1985).
J. S. Sisson, S. M. Prescott, T. M. McIntyre and G. A. Zimmerman. Production of platelet-activating factor by stimulated human polymorphonuclear leukocytes. J. Biol. Chem., 138:3918–3926 (1987).
S. L. Reinhold, G. A. Zimmerman, S. M. Prescott and T. M. McIntyre. Phospholipid remodeling in human neutrophiles. J. Biol.Chem., 264:21652–21659 (1989).
K. Hirata, M. Katayama, Y. Ohashi, R. Kuroda, M. Suematsu, S. Kawashima and M. Yokoyama. Activation and inhibition of nitric oxide synthase from cultured bovine aortic endotherial cells by phospholipids and arachidonic acid. Ann. N. Y. Acad. Sci., 748:555–558 (1995).
A. A. Steil, M. C. G. Rodriguez, A. Alonso, M. S. Crespo and L. Bosca. Platelet-activating factor: the effector of protein-rich plasma extravasation and nitric oxide synthase induction in rat immune complex peritonitis. Brit. J. Pharmacol., 114:895–901 (1995).
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Aramaki, Y., Arima, H., Hara, T. et al. Liposomal Induction of a Heat-stable Macrophage Priming Factor to Induce Nitric Oxide in Response to LPS. Pharm Res 13, 1389–1392 (1996). https://doi.org/10.1023/A:1016034303012
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DOI: https://doi.org/10.1023/A:1016034303012