title: Phospholipids modulate superoxide and nitric oxide production by lipopolysaccharide and phorbol 12-myristate-13-acetate-activated microglia.
abstract: Microglial activation and inflammatory processes have been implicated in the pathogenesis of a number of neurodegenerative disorders. Recently, peroxynitrite (ONOO(-)), the reaction product of superoxide (O(2)(-)) and nitric oxide (NO) both of which can be generated by activated microglia, has been demonstrated to act as a major mediator in the neurotoxicity induced by activated microglia. On the other hand, phospholipids such as phosphatidylserine (PS) and phosphatidylcholine (PC) have been reported to modulate the immune function of phagocytes. We therefore evaluated the effects of liposomes which comprise both PS and PC (PS/PC liposomes) or PC only (PC liposomes) regarding the production of both O(2)(-) and NO by lipopolysaccharide (LPS)/phorbol 12-myristate-13-acetate (PMA)-activated microglia using electron spin resonance (ESR) spin trap technique with a DEPMPO and Griess reaction, respectively. Pretreatment with PS/PC liposomes or PC liposomes considerably inhibited the signal intensity of O(2)(-) adduct associated with LPS/PMA-activated microglia in a dose-dependent manner. In addition, pretreatment with PS/PC liposomes also significantly reduced LPS/PMA-induced microglial NO production. In contrast, pretreatment with PC liposomes had no effect on the NO production. These results indicate that PS/PC liposomes can inhibit the microglial production of both NO and O(2)(-), and thus presumably prevent a subsequent formation of ONOO(-). Therefore, PS/PC liposomes appear to have both neuroprotective and anti-oxidative properties through the inhibition of microglial activation.
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medicine, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan. hashioka@interchange.ubc.ca
authors.forename: Sadayuki
authors.initials: S
authors.lastname: Hashioka
authors.forename: Youn-Hee
authors.initials: YH
authors.lastname: Han
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Fujii
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kato
authors.forename: Akira
authors.initials: A
authors.lastname: Monji
authors.forename: Hideo
authors.initials: H
authors.lastname: Utsumi
authors.forename: Makoto
authors.initials: M
authors.lastname: Sawada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakanishi
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Kanba
mesh_terms: D000818:Animals; D002460:Cell Line; D004578:Electron Spin Resonance Spectroscopy; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009569:Nitric Oxide / Q000096:biosynthesis*; D010587:Phagocytosis; D010743:Phospholipids / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D008070:Lipopolysaccharides; D010743:Phospholipids; D013481:Superoxides; D009569:Nitric Oxide; D013755:Tetradecanoylphorbol Acetate