MINIMALLY MODIFIED LOW-DENSITY-LIPOPROTEIN INDUCES MONOCYTE CHEMOTACTIC PROTEIN-1 IN HUMAN ENDOTHELIAL-CELLS AND SMOOTH-MUSCLE CELLS
MINIMALLY MODIFIED LOW-DENSITY-LIPOPROTEIN INDUCES MONOCYTE CHEMOTACTIC PROTEIN-1 IN HUMAN ENDOTHELIAL-CELLS AND SMOOTH-MUSCLE CELLS
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DOI：
10.1073/pnas.87.13.5134
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发表时间：
1990-07-01
影响因子：
11.1
通讯作者：
FOGELMAN, AM
中科院分区：
文献类型：
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作者：
CUSHING, SD;BERLINER, JA;FOGELMAN, AM
暴露于氧化修饰过的低密度脂蛋白（LDL） （MM-LDL）后，单独或一起培养的人内皮细胞（EC）和平滑肌细胞（SMC）产生的单核细胞趋化活性比对照细胞或暴露于新分离LDL的细胞高2- 3倍。单核细胞趋化活性的增加与单核细胞趋化蛋白1 (MCP-1) mRNA水平的增加是平行的，MCP-1是由人胶质瘤U-105MG细胞系组成的。制备的抗培养狒狒平滑肌细胞趋化因子（anti-SMCF）抗体对细菌趋化因子f-Met-Leu-Phe诱导的单核细胞迁移无抑制作用。然而，在暴露于MM-LDL前后，抗smcf完全抑制U-105MG细胞、EC和SMC培养基中的单核细胞趋化活性。此外，暴露于MM-LDL的EC和SMC共培养的单核细胞向内皮下空间的迁移被抗smcf完全抑制。抗smcf特异性免疫沉淀来自EC的10-kDa和12.5 kda蛋白。将[35S]蛋氨酸掺入免疫沉淀蛋白中，与MM-LDL刺激EC培养基中单核细胞趋化活性和EC中MCP-1 mRNA水平相似。我们得出结论：(i) SMCF实际上是MCP-1， （ii） MCP-1是由MM-LDL诱导的。
After exposure to low density lipoprotein (LDL) that had been minimally modified by oxidation (MM-LDL), human endothelial cells (EC) and smooth muscle cells (SMC) cultured separately or together produced 2- to 3-fold more monocyte chemotactic activity than did control cells or cells exposed to freshly isolated LDL. This increase in monocyte chemotactic activity was paralleled by increases in mRNA levels for a monocyte chemoatactic protein 1 (MCP-1) that is constitutively produced by the human glioma U-105MG cell line. Antibody that had been prepared against cultured baboon smooth muscle cell chemotactic factor (anti-SMCF) did not inhibit monocyte migration induced by the potent bacterial chemotactic factor f-Met-Leu-Phe. However, anti-SMCF completely inhibited the monocyte chemotactic activity found in the media of U-105MG cells, EC, and SMC before and after exposure to MM-LDL. Moreover, monocyte migration into the subendothelial space of a coculture of EC and SMC that had been exposed to MM-LDL was completely inhibited by anti-SMCF. Anti-SMCF specifically immunoprecipitated 10-kDa and 12.5-kDa proteins from EC. Incorporation of [35S]methionine into the immunoprecipitated proteins paralleled the monocyte chemotactic activity found in the medium of MM-LDL stimulated EC and the levels of MCP-1 mRNA found in the EC. We conclude that (i) SMCF is in fact MCP-1 and (ii) MCP-1 is induced by MM-LDL.