title: Elevated serum levels of arachidonoyl-lysophosphatidic acid and sphingosine 1-phosphate in systemic sclerosis.
abstract: Systemic sclerosis (SSc) is an often fatal disease characterized by autoimmunity and inflammation, leading to widespread vasculopathy and fibrosis. Lysophosphatidic acid (LPA), a bioactive phospholipid in serum, is generated from lysophospholipids secreted from activated platelets in part by the action of lysophospholipase D (lysoPLD). Sphingosine 1-phosphate (S1P), a member of the bioactive lysophospholipid family, is also released from activated platelets. Because activated platelets are a hallmark of SSc, we wanted to determine whether subjects with SSc have altered serum lysophospholipid levels or lysoPLD activity. Lysophospholipid levels were measured using mass spectrometric analysis. LysoPLD activity was determined by quantifying choline released from exogenous lysophosphatidylcholine (LPC). The major results were that serum levels of arachidonoyl (20:4)-LPA and S1P were significantly higher in SSc subjects versus controls. Furthermore, serum LPA:LPC ratios of two different polyunsaturated phospholipid molecular species, and also the ratio of all species combined, were significantly higher in SSc subjects versus controls. No significant differences were found between other lysophospholipid levels or lysoPLD activities. Elevated 20:4 LPA, S1P levels and polyunsaturated LPA:LPC ratios may be markers for and/or play a significant role in the etiology of SSc and may be future pharmacological targets for SSc treatment.
authors.affiliation: Department of Health Chemistry, Institute of Health Bioscience, The University of Tokushima Graduate School, 1-78-1 Shomachi, Tokushima 770-8505, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Tokumura
authors.forename: Laura D
authors.initials: LD
authors.lastname: Carbone
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Yoshioka
authors.forename: Junichi
authors.initials: J
authors.lastname: Morishige
authors.forename: Masaki
authors.initials: M
authors.lastname: Kikuchi
authors.forename: Arnold
authors.initials: A
authors.lastname: Postlethwaite
authors.forename: Mitchell A
authors.initials: MA
authors.lastname: Watsky
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008246:Lysophospholipids / Q000097:blood*; D008875:Middle Aged; D010727:Phosphoric Diester Hydrolases / Q000097:blood*; D012595:Scleroderma, Systemic / Q000097:blood* / Q000276:immunology; D013110:Sphingosine / Q000031:analogs & derivatives / Q000097:blood; D055815:Young Adult; D000099189:Lysophospholipase D
chemical_list: D008246:Lysophospholipids; D010727:Phosphoric Diester Hydrolases; D013110:Sphingosine; D000099189:Lysophospholipase D; C060506:sphingosine 1-phosphate; C032881:lysophosphatidic acid