Upregulation of SR-PSOX/CXCL16 and recruitment of CD8+ T cells in cardiac valves during inflammatory valvular heart disease.

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-gamma (IFN-gamma) 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-gamma production by CD8+ T cells during inflammatory valvular heart disease.