Role of Monocyte Chemoattractant Protein-1 in Various Pathological Conditions

单核细胞趋化蛋白-1 在各种病理条件下的作用

• 批准号: 08457073
• 负责人: TAKEYA Motohiro
• 金额: $ 3.9万
• 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 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457073/
• 关键词: MCP-1; monoclonal antibody; TRPM-3-positive macrophages; lung granulomatosis; nitric oxide; rat collagen arthritis; rat crescentic glomerulonephritis; squamous metaplasia; 間質性肺炎; 免疫組織化学; 単球・マックロファージ; TRPM-3陽性マクロファージ; コラーゲン関節炎; HTLV-1 associat

Monocyte chemoattractant protein-1 (MCP-1) is one of the most potent chemoattractants for monocytes which belongs to the C-C chemokine group. In this project, we clarified the crucial role of MCP-1 in various pathological conditions in rats.1.Injection of recombinant rat MCP-1 into rat skin induced infiltration of TRPM-3-positive activated macrophages, whereas ED2-positive resident macrophages did not accumulate to the injection site.2.In rat models of pulmonary granulomatosis, we confirmed the expression of MCP-1 in the early phase of inflammation. Administration of nitric oxide synthase inhibitors significantly suppressed nitric oxide (NO) production and resulted in marked reduction monocyte/macrophage infiltration as well as in inhibition of MCP-1 production. These data indicate that NO may induce MCP-1 expression in lung granulomatosis.3.In collagen-induced rat arthritis, both MCP-1 concentration in the joint lavages and MCP-1 mRNA levels in the joint tissues at 2 weeks after the i … More mmunization of collagen. Injection of an anti-rat MCP-1 monoclonal antibody significantly decreased the number of exudate macrophages in the lesions and reduced the ankle swelling by about 30% compared with controls. These results suggest that MCP-1 plays a critical role in the recruitment of monocytes and in the development of rat arthritis.4.IN crescentic glomeruionephritis in rats, MCP-1 mRAN and proein are paralleled with the infiltration of monocyte/macrophages into glomeruli. MCP-1 mRNA was expressed intensely in the glomeruli 4days after the anti-glomerular basement membrane antibody injection. When MCP-1 was neutralized with anti-MCP-1 antibody administration, the number of monocyte/macrophage infiltrating in the glomeruli decreased by 34.7% and proteinuria by 66.4% at day 4. These data suggest that MCP-1 plays a crucial role in the glomerular accumulation of monocyte/macrophages and that the infiltrating monocyte/macrophages cause glomerular injury and increased excretion of protein in the urine. Less

单核细胞趋化蛋白-1（MCP-1）是C-C趋化因子家族中最强的趋化因子之一。本研究旨在阐明MCP-1在大鼠各种病理状态中的重要作用：1.将重组大鼠MCP-1注射到大鼠皮肤中，可诱导TRPM-3阳性的活化巨噬细胞浸润，而ED 2阳性的驻留巨噬细胞不聚集到注射部位; 2.在大鼠肺肉芽肿模型中，我们证实MCP-1在炎症早期表达。一氧化氮合酶抑制剂的管理显着抑制一氧化氮（NO）的生产，并导致显着减少单核细胞/巨噬细胞浸润，以及在MCP-1的生产抑制。提示NO可诱导肺肉芽肿组织中MCP-1的表达。3.在胶原诱导的大鼠关节炎模型中，NO诱导2周后，关节灌洗液中MCP-1的浓度和关节组织中MCP-1 mRNA的水平均显著高于对照组，但NO诱导2周后，关节灌洗液中MCP-1的浓度和关节组织中MCP-1 mRNA的水平均显著低于对照组，而NO诱导2周后，关节灌洗液中MCP-1的浓度和关节组织中MCP-1 mRNA的水平均显著高于对照组。 ...更多信息 胶原蛋白的免疫。与对照组相比，注射抗大鼠MCP-1单克隆抗体显著减少了病变中渗出巨噬细胞的数量，并使踝关节肿胀减少了约30%。这些结果表明MCP-1在单核细胞的募集和大鼠关节炎的发展中起关键作用。4.在大鼠新月体肾炎中，MCP-1 mRAN和蛋白与单核细胞/巨噬细胞向肾小球的浸润有关。注射抗肾小球基底膜抗体后4d，肾小球内MCP-1 mRNA表达增强。当MCP-1被抗MCP-1抗体中和时，肾小球中浸润的单核细胞/巨噬细胞的数量在第4天减少了34.7%，蛋白尿减少了66.4%。这些数据表明MCP-1在单核细胞/巨噬细胞的肾小球积累中起关键作用，并且浸润的单核细胞/巨噬细胞引起肾小球损伤和尿中蛋白质排泄增加。少

项目成果

Yamashiro S et al.: "Intradermal injection of monocyte chemoattractant protein-1 induces emigration and differentition of blood monocytes in rat skin" Int Arch Allergy Immunol. 115. 15-23 (1998)

Yamashiro S 等人：“皮内注射单核细胞趋化蛋白-1 诱导大鼠皮肤中血液单核细胞的迁移和分化”Int Arch Allergy Immunol。

Takeya M.et al: "Immunophenotypic characterization of macrophages migrate after intradermal injection of monocyte chemoattractant protein-1 (MCP-1) in rats." Acta Histochem Cytochem. 29. 208-209 (1996)

Takeya M.等人：“大鼠皮内注射单核细胞趋化蛋白-1 (MCP-1) 后巨噬细胞迁移的免疫表型特征。”

Yamamoto T.et al: "Morphological alteration of cultured tracheobronchial epithelial cells is accompanied by the expression of chemokines, MCP-1 and CINC/gro, in rats." Int J Exp Pathol. (in press). (1998)

Yamamoto T.等人：“大鼠中培养的气管支气管上皮细胞的形态变化伴随着趋化因子 MCP-1 和 CINC/gro 的表达。”

Takeya M et al.: "Immunophenotypic characterization of macrophages migrated after intradermal injection of monocyte chemoattractant protein-1 (MCP-1) in rats" Acta Histochem Cytochem. 29(sup). 208-209 (1996)

Takeya M 等人：“大鼠皮内注射单核细胞趋化蛋白-1 (MCP-1) 后巨噬细胞迁移的免疫表型特征”Acta Histochem Cytochem。

Iyonaga K.et al: "A novel monoclonal antibody, RM-4, specifically recognizes rat macrophages and dendritic cells in formalin-fixed paraffin-embedded tissues" Histochem J. 29. 105-116 (1997)

Iyonaga K.等人：“一种新型单克隆抗体 RM-4，可特异性识别福尔马林固定石蜡包埋组织中的大鼠巨噬细胞和树突状细胞” Histochem J. 29. 105-116 (1997)