Internalization and degradation of receptor bound C-reactive protein by U-937 cells: induction of H2O2 production and tumoricidal activity.
Internalization and degradation of receptor bound C-reactive protein by U-937 cells: induction of H2O2 production and tumoricidal activity.
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U-937 细胞受体结合 C 反应蛋白的内化和降解：诱导 H2O2 产生和杀肿瘤活性。
DOI：
10.1016/0167-4889(91)90101-3
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Mortensen,RF
中科院分区：
文献类型：
--
作者：
Tebo,JM;Mortensen,RF
人单核细胞系U-937上C反应蛋白（CRP-R）的膜受体的存在是确定受体结合配体的代谢命运和细胞对CRP的功能反应的基础。通过用链霉蛋白酶去除细胞表面结合的[125 I]CRP来测量内化的[125 I] CRP。将细胞加热至37°C导致约100个细胞的内化。50%的受体结合[125 I]CRP或受体结合[125 I]CRP-PC-KLH复合物。U-937细胞将约25%的内化[125 I]CRP降解为TCA可溶性放射性标记产物。溶酶体营养剂（氯喹，NH 4Cl）大大降低了CRP降解的程度，而不改变结合或内化。此外，pH < 4.0导致受体结合的[125 I]CRP解离。用莫能菌素（一种阻止受体再循环的羧基离子载体）处理U-937细胞，导致内化的[125 I]CRP蓄积。因此，似乎CRP-R复合物被内化到内体区室中，其中CRP与其受体解偶联并随后降解。CRP启动了U-937细胞的分化，使其获得了产生H2 O2的能力，并显示出体外杀肿瘤活性。结果支持CRP的内化和降解导致炎症期间单核细胞活化的概念。
The presence of a membrane receptor for C-reactive protein (CRP-R) on the human monocytic cell line U-937 was the basis for determining the metabolic fate of the receptor-bound ligand and the functional response of the cells to CRP. Internalized [125I]CRP was measured by removing cell surface-bound [125I]CRP with pronase. Warming cells to 37°C resulted in the internalization of approx. 50% of the receptor-bound [125I]CRP or receptor-bound [125I]CRP-PC-KLH complexes. U-937 cells degraded about 25% of the internalized [125I]CRP into TCA-soluble radiolabeled products. The lysosomotrophic agents (chloroquine, NH4Cl) greatly decreased the extent of CRP degradation without altering binding or internalization. In addition, a pH < 4.0 resulted in dissociation of receptor-bound [125I]CRP. Treatment of U-937 cell with monensin, a carboxylic ionophore which prevents receptor recycling, resulted in accumulation of internalized [125I]CRP. Therefore, it appears that the CRP-R complex is internalized into an endosomal compartment where the CRP is uncoupled from its receptor and subsequently degraded. CRP initiated the differentiation of the U-937 cells so that they acquired the ability to produce H2O2and also display in vitro tumoricidal activity. The results support the concept that internalization and degradation of CRP leads to the activation of monocytes during inflammation.