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(Circulation Research. 1997;80:638-644.)
© 1997 American Heart Association, Inc.

Articles

Lysophosphatidylcholine Increases Expression of Heparin-Binding Epidermal Growth Factor–Like Growth Factor in Human T Lymphocytes

Eiichiro Nishi, Noriaki Kume, Hiroshi Ochi, Hideaki Moriwaki, Yoshio Wakatsuki, Shigeki Higashiyama, Naoyuki Taniguchi, , Toru Kita

From the Department of Geriatric Medicine (E.N., N.K., H.O., H.M., Y.W., T.K.), Graduate School of Medicine, Kyoto University, Kyoto, Japan, and the Department of Biochemistry (S.H., N.T.), Osaka University Medical School, Osaka, Japan.

Correspondence to Noriaki Kume, MD, PhD, Instructor, Department of Geriatric Medicine, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606, Japan. E-mail nkume{at}kuhp.kyoto-u.ac.jp

Abstract Atherosclerotic lesions contain substantial numbers of activated T lymphocytes in addition to monocytes/macrophages. T cell–derived cytokines and growth factors may play a role in atherogenesis; however, stimuli responsible for T-cell activation in atherogenesis have not been fully elucidated. In this study, we provide evidence that lysophosphatidylcholine (lyso-PC), a polar phospholipid component increased in atherogenic lipoproteins and atherosclerotic lesions, can upregulate gene expression and secretion of heparin-binding epidermal growth factor–like growth factor (HB-EGF) in cultured T lymphocytes isolated from human peripheral blood. Effects of lyso-PC on T lymphocytes appear to be selective and specific, since lyso-PC also increases interleukin (IL)-2 receptor expression but does not affect mRNA levels for IL-2 or IL-4. Lyso-PC–induced upregulation of HB-EGF and IL-2 receptor mRNA in peripheral T cells is mostly dependent on exogenous IL-2 in conditioned medium. The effect of lyso-PC on HB-EGF induction was more potent in CD4⁺ cells than in CD8⁺ cells, although lyso-PC increases IL-2 receptor expression dramatically in both CD4⁺ cells and CD8⁺ cells. Lyso-PC similarly increased HB-EGF expression in Jurkat cells, a cell line for human CD4⁺ T lymphocytes. These results in vitro suggest that lyso-PC may be an important stimulus for T cells in atherogenesis in vivo to upregulate HB-EGF and that T cell–derived smooth muscle growth factors may modulate atherosclerotic progression.

Key Words: lysophosphatidylcholine • heparin-binding epidermal growth factor–like growth factor • T lymphocyte

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