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Int J Med Sci 2009; 6(4):168-176. doi:10.7150/ijms.6.168

Research Paper

Elevated Serum Levels of Arachidonoyl-lysophosphatidic Acid and Sphingosine 1-Phosphate in Systemic Sclerosis

Akira Tokumura1, Laura D. Carbone2,3, Yasuko Yoshioka1, Junichi Morishige1, Masaki Kikuchi1, Arnold Postlethwaite2,3, Mitchell A. Watsky4 ✉

1. Department of Health Chemistry, Institute of Health Bioscience, The University of Tokushima Graduate School, 1-78-1 Shomachi, Tokushima 770-8505, Japan;
2. Veterans Affairs Medical Center, Memphis, Tennessee, USA;
3. Division of Rheumatology, Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA;
4. Department of Physiology, University of Tennessee Health Science Center, 894 Union Ave., Memphis, Tennessee, USA

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.

Keywords: scleroderma, lysophospholipids, LPA, S1P, LPC, lysophospholipase D, fibrosis

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How to cite this article:
Tokumura A, Carbone LD, Yoshioka Y, Morishige J, Kikuchi M, Postlethwaite A, Watsky MA. Elevated Serum Levels of Arachidonoyl-lysophosphatidic Acid and Sphingosine 1-Phosphate in Systemic Sclerosis. Int J Med Sci 2009; 6(4):168-176. doi:10.7150/ijms.6.168. Available from http://www.medsci.org/v06p0168.htm