| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2003: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
|---|
| Research Abstract |
Macrophages play a major role in the development of vascular lesions in atherogenesis. The cells express FcγRIIIa(CD16) identical to that in NK cells, but with a cell type-specific glycosylation. The FcγRIIIa are released from the cell surface on activation, and these soluble forms (sFcγRIIIa) are present in plasma. We measured sFcγRIIIa^<M_Φ> derived from macrophages in plasma with Immuno-PCR with anti-FcγRIII mAb,MKGR14(mlgM), which recognizes FcγRIIIa^<M_Φ> specifically. In healthy volunteers, the level of sFcγRIIIa^<M_Φ> increased with ageing, and positively correlated with serum LDL-cholesterol to HDL-cholesterol ratios and LDL-cholesterol, but negatively with HDL-cholesterol. In addition, the sFcγRIIIa^<M_Φ> level was related to the number of risk factors for atherosclerosis and correlated with carotid maximum intima-media thickness(IMT) in subjects with annual medical checkup. In contrast, the level of sFcγRIIIa(sFcγRIIIa^<M_Φ> plus sFcγRIIIa^<NK>) correlated with the number of NK cells in peripheral blood, and the level of total sFcγRIII(sFcγRIIIa plus sFcγRIIIb) correlated with the number of neutrophils. In patients undergoing coronary angiography, the levels of these sFcγRIIIs were significantly increased in patients with coronary artery diseases(CAD) with atherosclerosis, but not in patients with vasospastic angina(VSA) or intact coronary artery, compared with age-matched healthy donors. The sFcγRIIIa^<M_Φ> level was related to the number of significant coronary artery stenoses, and positively correlated with LDL-cholesterol to HDL-cholesterol ratios and lipoprotein(a), but negatively with HDL-cholesterol. No correlation among the levels of three sFcγRIIIs was observed in CAD patients, as well as in healthy donors. These findings may show that the macrophages are activated during the incipient stage of atherosclerosis, and that sFcγRIIIa^<M_Φ> may serve as predictive marker for atherosclerosis.
|
