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Vascular Biology |
From the Department of Cardiovascular Medicine (R.Y., N.K., T.K.), Graduate School of Medicine, Kyoto University, Kyoto, Japan; the Department of Social Service (M.T.), Kyoto University Hospital, Kyoto, Japan; the Department of Geriatric Medicine (M.T., M.M., T.K., K.T.), Graduate School of Medicine, Kyoto University, Kyoto, Japan; the Institute for Viral Research (T.S., S.Y.), Kyoto University, Kyoto, Japan; Biomedical Research Laboratories (S.T., J.Y.), Sankyo Co., Ltd, Tokyo, Japan; the Department of Cardiovascular Surgery (T.N., M.K.), Graduate School of Medicine, Kyoto University, Kyoto, Japan; and the Department of Anatomic Pathology (M.K., T.M.), Kyoto University Hospital, Kyoto, Japan.
Correspondence to Dr Makoto Tanaka, Department of Social Service, Kyoto University Hospital, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. E-mail makoto{at}kuhp.kyoto-u.ac.jp
Objective SR-PSOX/CXCL16 is a transmembrane chemokine and is implicated in activated CD8+ T cell trafficking. In the present study, we examined the expression pattern of SR-PSOX/CXCL16 in the heart and investigated a potential role of SR-PSOX/CXCL16 in inflammatory valvular heart disease.
Methods and Results Initial expression of SR-PSOX/CXCL16 in murine embryos was detected in endothelial cells lining endocardial cushions in the forming heart at E11.5. From mid-gestation to adult, expression of this gene in the heart was exclusively observed in valvular endothelial cells. Examination of SR-PSOX/CXCL16 expression in human cardiac valves demonstrated that SR-PSOX/CXCL16 was strongly expressed in valvular and neocapillary endothelial cells in patients with infective endocarditis. SR-PSOX/CXCL16 expression in neocapillary endothelial cells was also observed in patients with rheumatic and atherosclerotic valvular disease. Moreover, CD8+ T cells were distributed closely to endothelial cells expressing SR-PSOX/CXCL16. In vitro adhesion assays showed that SR-PSOX/CXCL16 induced adhesion of activated CD8+ T cells to vascular cell adhesion molecule-1 (VCAM-1) through very late antigen-4 (VLA-4) activation. Furthermore, SR-PSOX/CXCL16 stimulated interferon-
(IFN-
) production by CD8+ T cells.
Conclusions SR-PSOX/CXCL16 may be involved in CD8+ T cell recruitment through VLA-4 activation and stimulation of IFN-
production by CD8+ T cells during inflammatory valvular heart disease.
Key Words: SR-PSOX/CXCL16 cardiac valve endothelial cell infective endocarditis CD8+ T cell
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