title: Fluctuation of lysosomal phospholipase A2 in experimental autoimmune uveitis in rats.
abstract: Intraocular inflammation leads to oxidative stress and may generate lipid oxidation products. The present study was conducted to elucidate the pathophysiological roles of the lysosomal phospholipase A2 (LPLA2), a phospholipid-degrading enzyme, and the production of oxidized phospholipids (oxPLs) in autoimmune uveitis using a rat model. Lewis rats were immunized with a bovine interphotoreceptor retinoid-binding protein (bIRBP) peptide with complete Freund's adjuvant (CFA) to induce experimental autoimmune uveitis (EAU). The aqueous humor (AH) and serum were collected every week for 4 weeks from the immunized rats. The LPLA2 activity of the AH and serum was detected using liposomes consisting of 1,2-dioleoylphosphatidylglycerol/N-acetylsphingosine as the substrate under acidic conditions. Immunohistochemical analysis was performed using antibodies against LPLA2 and oxPLs. The ocular inflammation was exacerbated at 2 weeks after immunization. The LPLA2 activity in the rat AH was increased by EAU induction, and was concomitant with the extent of inflammation in the anterior chamber (AC). In contrast, the LPLA2 activity in the rat serum was not influenced by EAU induction. At 2 weeks after immunization, immunoreactivity of LPLA2 was observed in infiltrated macrophages in the AC and vitreous cavity of the EAU rats. Furthermore, immunoreactivity of oxPLs was observed in the infiltrated macrophages of EAU rat eyes. These results demonstrated that the LPLA2 activity of the AH is augmented with the inflammation in the AC. The high expression of LPLA2 and production of oxPLs are found in the infiltrated macrophages in the acute inflammation of EAU rats. The present findings suggest the connection between LPLA2 activity and oxPL metabolism in the inflammation sites in the eye.
authors.affiliation: Department of Ophthalmology, School of Medicine, Sapporo Medical University, Sapporo, Hokkaido 060-8543, Japan.
authors.forename: Ei
authors.initials: E
authors.lastname: Ohkawa
authors.affiliation: Department of Ophthalmology, School of Medicine, Sapporo Medical University, Sapporo, Hokkaido 060-8543, Japan. Electronic address: mikihira@sapmed.ac.jp.
authors.forename: Miki
authors.initials: M
authors.lastname: Hiraoka
authors.affiliation: Department of Ophthalmology, School of Medicine, Sapporo Medical University, Sapporo, Hokkaido 060-8543, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Abe
authors.affiliation: Department of Pathology, School of Medicine, Sapporo Medical University, Sapporo, Hokkaido 060-8543, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Murata
authors.affiliation: Department of Ophthalmology, School of Medicine, Sapporo Medical University, Sapporo, Hokkaido 060-8543, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohguro
mesh_terms: D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008247:Lysosomes; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D018384:Oxidative Stress; D054467:Phospholipases A2 / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D014605:Uveitis / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism*
chemical_list: D054467:Phospholipases A2
keywords: Aqueous humor; Experimental autoimmune uveitis; Lewis rats; Lysosomal phospholipase A2; Macrophages; Oxidative stress; Oxidized phospholipids