MANIPULATION OF INFLAMMATORY RESPONSES BY MODULATION OF MACROPHAGE FUNCTIONS.

通过调节巨噬细胞功能来控制炎症反应。

• 批准号: 10670189
• 负责人: IWABUCHI Kazuya
• 金额: $ 1.41万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670189/
• 关键词: MACROPHAGE; INFLAMMATION; TYROSINE KINASE; MIF; MCP-1; TRANSGENIC MICE; ATHEROSCLEROSIS; AIF-1; MCP―1; アログラフト炎症因子―1; チロシンリン酸化; アンチセンス; 肉芽腫

Overexpression of Csk in a macrophage cell line, J774A.1, resulted in reduced productions of nitric oxide and monokines with reduced rates of phagocytosis and acetyl-LDL uptake. The transfectants also demonstrated enhanced production of PGEィイD22ィエD2. Somatic transgenesis with csk-gene into macrophages may be applicable to some diseases, in which macrophages may play important roles, such as hemophagocytic syndrome, demyelinating diseases, and atherosclerosis. Functional modulation of macrophages could be also achieved by inter-ferring macrophage migration inhibitory factor (MIF) with the anti-MIF antibody in rodents model of uveoretinitis, by either overexpressing or downregulating allograft inflammatory factor (AIF)-1 in atherosclerosis model mice, ApoEィイD1-/-ィエD1. Studies with MCP-1 transgenic mice revealed that MCP-1 plays critical roles in contact hypersensitivity responses by facilitating a migration of Langerhans cells in the skin and in endotoxemia via regulations of cytokine productions. Ath 7, a genetic locus which represent a resistance to atherosclerosis was shown to be expressed by macrophages. Bone marrow transplantation from resistant strains into ApoEィイD1-/-ィエD1 was shown to be a prominsing a strategy for a therapeutics.

Csk在巨噬细胞系J774A.1中的过表达导致一氧化氮和单核因子的产生减少，吞噬作用和乙酰-LDL摄取率降低。转染子还证明了PGE β D22 β D2的产生增强。体细胞转基因巨噬细胞可用于治疗噬血细胞综合征、脱髓鞘疾病和动脉粥样硬化等巨噬细胞可能发挥重要作用的疾病。巨噬细胞的功能调节也可以通过在葡萄膜视网膜炎的啮齿动物模型中用抗-MIF抗体干扰巨噬细胞移动抑制因子（MIF），通过在动脉粥样硬化模型小鼠中过表达或下调同种异体移植炎性因子（AIF）-1（ApoE β D1-/-β D1）来实现。对MCP-1转基因小鼠的研究表明，MCP-1通过促进皮肤中朗格汉斯细胞的迁移在接触性超敏反应中起关键作用，并通过调节细胞因子的产生在内毒素血症中起关键作用。巨噬细胞表达抗动脉粥样硬化基因座Ath 7。将耐药菌株的骨髓移植到ApoEイD1-/-D1中已被证明是一种突出的治疗策略。

项目成果

岩淵和也: "NKT細胞の分化と機能"アレルギー科. 6. 9-16 (1998)

Kazuya Iwabuchi：“NKT 细胞的分化和功能”过敏系 6. 9-16 (1998)。

Naoto Matsuki: "Prevention of infection of influenza virus in DQ6 mice,a human model,by a peptide vaccine prepared according to the cassette theory"Vaccines. 17. 1161-1168 (1999)

Naoto Matsuki：“通过根据盒式理论制备的肽疫苗预防人类模型 DQ6 小鼠感染流感病毒”疫苗。

Nobuyoshi Kitaichi: "Inhibition of experimental autoimmune uveoretinitis with anti-macrophage migration inhibitory factor antibodies"Current Eye Research. 20. 109-114 (2000)

Nobuyoshi Kitaichi：“用抗巨噬细胞迁移抑制因子抗体抑制实验性自身免疫性葡萄膜视网膜炎”当前眼科研究。

Akio Takahashi: "Development of peptide vaccines inducing production of neutralizing antibodies against HIV-1 viruses in HLA-DQ6 mice."Vaccine. 16(16). 1537-1543 (1998)

Akio Takahashi：“开发肽疫苗，诱导 HLA-DQ6 小鼠产生针对 HIV-1 病毒的中和抗体。”疫苗。

Takako Kizaki: "An increase in basal glucoeorticoid concentration with age induces suppressor macrephage with high density FcγRII/III."Immunology. 93(3). 409-414 (1998)

Takako Kizaki：“基础糖皮质激素浓度随年龄的增加会诱导具有高密度 FcγRII/III 的抑制性巨噬细胞。”免疫学 93(3) (1998)。