CELLULAR ACTIVATION OF LATENT TRANSFORMING GROWTH-FACTOR-BETA REQUIRES BINDING TO THE CATION-INDEPENDENT MANNOSE 6-PHOSPHATE INSULIN-LIKE GROWTH-FACTOR TYPE-II RECEPTOR
CELLULAR ACTIVATION OF LATENT TRANSFORMING GROWTH-FACTOR-BETA REQUIRES BINDING TO THE CATION-INDEPENDENT MANNOSE 6-PHOSPHATE INSULIN-LIKE GROWTH-FACTOR TYPE-II RECEPTOR
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DOI：
10.1073/pnas.88.2.580
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发表时间：
1991-01-01
影响因子：
11.1
通讯作者：
RIFKIN, DB
中科院分区：
文献类型：
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作者：
DENNIS, PA;RIFKIN, DB
通常在牛主动脉内皮细胞和牛平滑肌细胞的共培养物中观察到的潜伏性转化生长因子β（LTGF-β）的活化可以通过将细胞与甘露糖6-磷酸（Man-6-P）或针对阳离子非依赖性Man-6-P/胰岛素样生长因子II型受体（抗Man-6-PR）的抗体共培养来抑制。通过测量共培养条件培养基（用或不用Man-6-P或抗Man-6-PR形成）抑制牛主动脉内皮细胞迁移和蛋白酶产生的能力来确定该结果，所述活性先前显示与转化生长因子β活性相关。Man-6-P的抑制是剂量依赖性的，在100 μ M时观察到最大抑制，并且是特异性的，因为甘露糖1-磷酸和葡萄糖6-磷酸不干扰LTGF-β的活化。抗Man-6-PR的抑制作用也是特异性的和剂量依赖性的;在400 μ g/ml时出现最大的激活抑制。对照实验表明，Man-6-P和抗Man-6-PR不干扰牛主动脉内皮细胞迁移的基础水平、加入外源性转化生长因子β时观察到的迁移、纤溶酶或瞬时酸化对转化生长因子β的激活以及LTGF-β的释放。因此，与阳离子非依赖性Man-6-P/胰岛素样生长因子II型受体的结合似乎是激活LTGF-β的必要条件。
The activation of latent transforming growth factor beta (LTGF-beta) normally seen in cocultures of bovine aortic endothelial and bovine smooth muscle cells can be inhibited by coculturing the cells with either mannose 6-phosphate (Man-6-P) or antibodies directed against the cation-independent Man-6-P/insulin-like growth factor type II receptor (anti-Man-6-PR). This result was established by measuring the ability of coculture conditioned medium (formed with or without Man-6-P or anti-Man-6-PR) to suppress bovine aortic endothelial cell migration and protease production, activities previously shown to be related to transforming growth factor beta activity. The inhibition by Man-6-P is dose dependent, with maximal inhibition seen at 100-mu-M, and is specific because mannose 1-phosphate and glucose 6-phosphate do not interfere with activation of LTGF-beta. The inhibitory effect of anti-Man-6-PR is also specific and dose dependent; maximal inhibition of activation occurs at 400-mu-g/ml. Control experiments indicate that Man-6-P and anti-Man-6-PR do not interfere with the basal level of migration of bovine aortic endothelial cells, the migration observed when exogenous transforming growth factor beta is added, the activation of transforming growth factor beta by plasmin or transient acidification, and the release of LTGF-beta. Thus, binding to the cation-independent Man-6-P/insulin-like growth factor type II receptor appears to be a requirement for activation of LTGF-beta.