Liposomes as immunomodulator--inhibitory effect of liposomes on NO production from macrophages.
Liposomes have been artificially made into membranous vesicles composed essentially of naturally occurring phospholipids and have been found to serve as a carrier of drugs and an immunological adjuvant. After being intravenously injected, they are quickly removed from the blood circulation and trapped by Kupffer cells of the liver and macrophages of spleen. However, the changes liposomes exert in these cells with which liposomes interact remain unresolved. To clarify this point is very important to assure the safe use of liposomes as drug carriers. Macrophages have many unique functions, and nitric oxide (NO) produced by NO synthase (NOS) which is induced in response to some cytokines and bacterial products such as lipopolysaccharide (LPS) is responsible for the bactericidal, tumoricidal and immune regulatory activities. On the other hand, overexpressed NO is implicated in the development of atherosclerosis, DNA injury, and hypotension associated with septic shock. This article focuses on the effects of liposomes on NO production from LPS-stimulated mice peritoneal macrophages in vitro; we found that liposomes composed of phosphatidylserine inhibit NO production. We also discuss the mechanism of the inhibitory activity of liposomes.
Aramaki
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School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan. aramaki@ps.toyaku.ac.jp
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D016166:Free Radical Scavengers / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008081:Liposomes / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009569:Nitric Oxide / Q000096:biosynthesis*
D000276:Adjuvants, Immunologic; D016166:Free Radical Scavengers; D008081:Liposomes; D009569:Nitric Oxide