KAIKITA Koichi Kumamoto University, Graduate School of Medical Sciences, Assistant, 大学院・医学薬学研究部, 助手 (30346978)
TERASAKI Yasuhiro Kumamoto University, Graduate School of Medical Sciences, Assistant, 大学院・医学薬学研究部, 助手 (50332870)
SAKASHITA Naomi Kumamoto University, Graduate School of Medical Sciences, Assistant Professor, 大学院・医学薬学研究部, 講師 (90284752)
|Budget Amount *help
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2003: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 2001: ¥4,300,000 (Direct Cost: ¥4,300,000)
Scavenger receptors (SRs) are a family of cell surface glycoproteins able to bind modified LDLs such as acetylated LDL and oxidized LDL. Currently, SR family molecules are classified into six groups, namely class A to class F. To examine the in vivo distribution and the roles of human class A scavenger receptor Type I, II (SR-AI,II), a prototype of SRs, we have produced highly-specific monoclonal antibodies. Using these antibodies, SR-AI,II was found to be expressed constitutionally on most tissue macrophages such as Kupffer cells of the liver, alveolar macrophages, sinushsitiocytes of lymph nodes and splenic red pulp macrophages. In pathological conditions, infiltrated macrophages in inflammatory tissues including those composing various kinds of granulomas, microglial cells in Alzheimer's disease, and lipid-laden macrophages in atherosclerosis were positively labeled. SR-AI,II expression was also found in 10-15 % of monocyte-derived dendritic cells treated with GM-CSF and IL-4. These results indicate that SR-AI,II plays important roles both in innate and acquired immunities as well as atherogenesis. Through these observations, SR-AI,II has been assigned as a new CD molecule, CD204, at VIIth Workshop of Human leukocyte Differentiation Antigen.
MARCO (macrophage receptor with a collagenous structure), an another member of Class A-SR, was reported to be induced by LPS stimulation. We have observed the induction of MARCO on Kupffer cells in non-alcoholic steatohepatitis, and shown that elevated endotoxin level in portal circulation induces MARCO in the liver. A project to disclose the role of MARCO in non-alcoholic steatohepatitis in now on progress.
To explore the role of LOX-1 (lectin-like oxidized LDL receptor-1), a class E SR, in atherogenesis, we have studied the lesion development using LOX-1-deficient mice. So far, however, no significant difference in lesion development compared to control mice has been observed.