|Budget Amount *help
¥3,500,000 (Direct Cost : ¥3,500,000)
Fiscal Year 2003 : ¥1,300,000 (Direct Cost : ¥1,300,000)
Fiscal Year 2002 : ¥2,200,000 (Direct Cost : ¥2,200,000)
Scavenger receptor for phosphatidylserine and oxidized lipoprotein (SR-PSOX) is a receptor for atherogenic oxidized LDL, which our group has identified in 2000. SR-PSOX turned out to be identical to CXCL16, which is a membrane-anchored chemokine for CXCR6.-positive lymphocytes. In this research project, we have found that interferon (IFN) gamma and oxidized LDL induce SR-PSOX/CXCL16 expression in macrophages, and that matrix metalloproteinases (MMP) 3 and 9, as well as an anti-apoptotic factor Bax, are colocalized with SR-PSOX/CXCL16 in human coronary and carotid atheoscierotic lesions, suggesting that SR-PSOX/CXCL16 may be involved in oxidized LDL-induced atherosclerotic plaque rupture. In addition, we have found that SR-PSOX/CXCL16 acts as a receptor for bacteria, as well as CXCR6-positive cells. Binding sites for oxidized LDL, bacteria and CXCR6 on the SR-PSOXICXCL16 molecule are located in the CXC chemokine domain and overlaped. Fractalkine (CX3CL1) is another membrane-anchored chemokine which also has a chemokine domain and a mucin domain, binds CX3CR1, but not oxidized LDL. Binding of CXCR6 to SR-PSOX/CXCL16 enhanced VLA-4-dependent adhesion to VCAM-1, indicating an outside-in signal transduction through CXCR6. Furthermore, SR-POSX/CXGL16 was also expressed in endothelial cells of inflammatory cardiac valves where CD8^+ lymphocytes were infiltrated, thus suggesting multiple roles of SR-PSOX/CXCL16 in a variety of diseases.