Pathological Significance of Macrophage Scavenger Receptors

巨噬细胞清道夫受体的病理意义

• 批准号: 08457071
• 负责人: TAKAHASHI Kiyoshi
• 金额: $ 4.54万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457071/
• 关键词: scavenger receptors; macrophages; atherosclerosis; foam cells; gene targeted mice; granuloma; immunohistochemistry; monoclonal antibodies; 免疫組織科学; ヒトMSR; 動脈硬化症; 免疫電顕; AGE; MSR knock out mouse; 修飾LDL; 細胞内動態

1. Anti-human monoclonal antibodies for macrophage scavenger receptors (MSR), as well as polyclonal antibodies for synthetic peptides of MSR, were generated in our laboratory. Using these antibodies, our immunohistochemical and immunoelectron microscopic studies demonstrated that MSR was distributed on the cell membranes of macrophages ubiquitously distributed in various organs and tissues of humans. Immunohistochemical and immunoelectron microscopic investigation with anti-bovine or anti-murine MSR monoclonal antibodies revealed similar distribution and subcellar localization of MSR in bovine and murine tissues.2. Our studies demonstrated in humans, bovines, and mice that MSR can bind to modified low density lipoproteins (LDL) such as acetylated LDL (acLDL) or oxidized LDL (oxLDL) and to advanced glycation end products (AGE). MSR-deficient mice revealed marked reductions in the uptake of acLDL, oxLDL, and AGE.3. In atheroselerotic lesions of human aorta, macrophage-derived foam cells showed the expression of MSR and intracellular accumulation of oxLDL and AGE.In apo-E/MSR double knockout mice and diet-induced LDL receptor/MSR double knockout mice, the lesion size of atheroselerosis was markedly reduced in the aorta, compared with apo-E or diet-induced LDL receptor-single knockout mice, indicating that MSR is deeply implicated in atherognesis.4. Compared with the wild-type mice, the hepatic granuloma formation induced by intravenous injection of heat-killed Corynebacterium parvum (C.parvum) was delayed and the uptake of C.parvum by Kupffer cells was markedly impaire in MSR-deficient mice, particularly in the early stage. These results indicate that MSR is involved in the defense mechanisms against exogenously invading bacteria.

1.本实验室制备了抗人巨噬细胞清道夫受体（MSR）的单克隆抗体和MSR合成肽的多克隆抗体。使用这些抗体，我们的免疫组织化学和免疫电镜研究表明，MSR分布在细胞膜上的巨噬细胞普遍分布在各种器官和组织的人。免疫组化和免疫电镜观察显示，MSR在牛和小鼠组织中的分布和亚细胞定位相似.我们的研究在人类、牛和小鼠中证明，MSR可以与修饰的低密度脂蛋白（LDL）如乙酰化LDL（acLDL）或氧化LDL（oxLDL）结合，并与晚期糖基化终产物（AGE）结合。MSR缺陷小鼠显示acLDL、oxLDL和AGE的摄取显著减少。在人主动脉粥样硬化病变中，巨噬细胞源性泡沫细胞表达MSR，并在细胞内聚集oxLDL和AGE，在apo-E/MSR双基因敲除小鼠和饮食诱导的LDL受体/MSR双基因敲除小鼠中，与apo-E或饮食诱导的LDL受体单基因敲除小鼠相比，主动脉粥样硬化病变的大小显著减小，表明MSR与动脉粥样硬化有密切关系.与野生型小鼠相比，MSR缺陷小鼠静脉注射热灭活的短小棒状杆菌（Corynebacterium parvum，C.parvum）诱导的肝肉芽肿形成延迟，Kupffer细胞对C.parvum的摄取明显减弱，尤其是在早期阶段。这些结果表明，MSR参与防御机制对外来入侵细菌。

项目成果

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Kiyoshi Takahashi 等人：“巨噬细胞清道夫受体”临床免疫学 30. 1153-1160 (1998)

竹屋元裕 他: "粥状動脈硬化とマクロファージ" 病理と臨床. 16. 1095-1099 (1998)

Motohiro Takeya 等人：“动脉粥样硬化和巨噬细胞”病理学和临床研究 16. 1095-1099 (1998)。

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