title: Increase of lysosomal phospholipase A2 in aqueous humor by uveitis.
abstract: This study was conducted to elucidate pathophysiological roles of the lysosomal phospholipase A2 (LPLA2), a phospholipid-degrading enzyme, of the aqueous humor (AH) in uveitis using an animal model and clinical specimens. Endotoxin-induced uveitis (EIU) was induced by subcutaneous injections of lipopolysaccharide from Escherichia coli to seven-week-old male Lewis rats. Inflammation of the anterior chamber (AC) was evaluated by measurement of the protein concentration of rat AH. The LPLA2 activity in the AH, serum and cerebrospinal fluid obtained from EIU rats was detected using liposomes consisting of 1,2-dioleoylphosphatidylglycerol/N-acetylsphingosine as the substrate under acidic conditions. Immunohistochemical analysis was performed using antibodies against CD11b and LPLA2. Sixty-five human AH specimens, in which 11 eyes had a history of chronic uveitis, were collected during patient cataract surgeries and used to determine LPLA2 activity. The LPLA2 activity in rat AH was significantly increased by EIU induction, and was correlated to the extent of inflammation in the AC. By contrast, the LPLA2 activity in rat serum or cerebrospinal fluid was not influenced by EIU induction. According to the immunohistochemistry, LPLA2 was found in CD11b positive cells in the AC of the EIU rats. In the clinical specimens, the AH obtained from the patients with a history of uveitis possessed significantly higher LPLA2 activity than that from the senile patients with cataract but without other ocular diseases. These results demonstrate that the LPLA2 activity in the AH is augmented with the inflammation in the AC and suggest that the LPLA2 in the AH participates in the inflammation process in the AC.
authors.affiliation: Department of Ophthalmology, School of Medicine, Sapporo Medical University, S1 W16 Chuo-ku, 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, S1 W16 Chuo-ku, Sapporo, Hokkaido 060-8543, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Abe
authors.affiliation: Department of Ophthalmology, School of Medicine, Sapporo Medical University, S1 W16 Chuo-ku, Sapporo, Hokkaido 060-8543, Japan; Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan.
authors.forename: Anton
authors.initials: A
authors.lastname: Lennikov
authors.affiliation: Department of Ocular Inflammation and Immunology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan; Department of Ophthalmology, Health Sciences University of Hokkaido, Sapporo, Hokkaido 002-8072, Japan.
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Kitaichi
authors.affiliation: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan; Department of Ocular Inflammation and Immunology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Ishida
authors.affiliation: Department of Ophthalmology, School of Medicine, Sapporo Medical University, S1 W16 Chuo-ku, Sapporo, Hokkaido 060-8543, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohguro
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001082:Aqueous Humor / Q000201:enzymology*; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008247:Lysosomes / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D054467:Phospholipases A2 / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D014605:Uveitis / Q000201:enzymology* / Q000473:pathology
chemical_list: D015415:Biomarkers; D054467:Phospholipases A2
keywords: aqueous humor; endotoxin-induced uveitis; lipid metabolism; phospholipase A2; uveitis