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Modification of cell surface glycocalyx by reactive oxygen species and its effect on cell adhesion

活性氧对细胞表面糖萼的修饰及其对细胞粘附的影响

基本信息

批准号：
11670119
负责人：
SUZUKI Keiichiro
金额：
$ 2.24万
依托单位：
Hyogo College of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670119/
关键词：
glycocalyx cell adhesion reactive oxygen species endothelial cell inflammation cancer metastasis sugar chain 好中球ヒドロキシルラジカル

项目摘要

The adhesion of colon cancer cells (colo201) and neutrophils to endothelial cells which had been briefly exposed to either hypoxanthine/xanthine oxidase, or hydrogen peroxide, or peroxynitrite was analyzed in the absence of de novo protein synthesis. Such treatments accelerated the adhesions of both colo201 cells and neutrophils to endothelial cells. In this study, de novo protein synthesis was blocked by AcD or CHX and no increase of E-selectin, P-selectin, ICAM-1 and thrombomodulin in endothelial cells was observed as judged by a FACS scan analysis using specific antibodies. Therefore, the accelerated cell adhesion is, most likely, due to the direct effect of hydroxyl radicals. These effects were blocked by SOD/catalase or EDTA.The results provided evidence that hydroxyl radicals affect the cell surface of endothelial cells and accelerate cell adhesion. These findings suggest that ROS may well accelerate cell adhesion very rapidly in the rolling of neutrophils or in the metastasis of tumor cells after radiation therapy or chemotherapy, both of which increase ROS production. ROS molecules have very short half lives and strong non-specific effects and as a result they may play an important role in the super acute phase of inflammation, ischemia-reperfusion or cancer metastasis through their effects on cell adhesion.Next we found that ceruloplasmin (Cp) can remove hydrogen peroxide and lipid hydroperoxide (LOOH) at physiological concentrations of reduced glutathione. The glutathione peroxidase-like activity of Cp together with its ferroxidase activity would completely remove the primary reactants required for both Fenton chemistry and lipid peroxidation. Moreover, Cp binds to extracellular myeloperoxidase (MPO) and prevents MPO making HOCl, a powerful oxidant which will lead to molecular damage. These two findings suggest that Cp may be an important antioxidant protein in lung lining fluid and extracellular spaces.

结肠癌细胞（colo 201）和嗜中性粒细胞的粘附内皮细胞已被短暂暴露于次黄嘌呤/黄嘌呤氧化酶，或过氧化氢，或过氧亚硝酸盐进行了分析，在从头蛋白质合成的情况下。这些处理加速了colo 201细胞和中性粒细胞与内皮细胞的粘附。在这项研究中，从头蛋白质合成被阻断的ACD或CHX和E-选择素，P-选择素，ICAM-1和血栓调节蛋白在内皮细胞中没有观察到增加，通过使用特异性抗体的FACS扫描分析判断。因此，加速的细胞粘附最有可能是由于羟基自由基的直接作用。这些作用可被SOD/过氧化氢酶或EDTA所阻断，为羟自由基影响内皮细胞表面并促进细胞粘附提供了证据。这些发现表明，ROS可以很好地加速细胞粘附非常迅速地在滚动的中性粒细胞或肿瘤细胞的转移后，放射治疗或化疗，这两个增加ROS的生产。ROS分子具有很短的半衰期和很强的非特异性作用，因此它们可能通过影响细胞粘附而在炎症、缺血再灌注或癌症转移的超急性期发挥重要作用。Cp的谷胱甘肽过氧化物酶样活性及其亚铁氧化酶活性将完全去除芬顿化学和脂质过氧化所需的主要反应物。此外，Cp与细胞外髓过氧化物酶（MPO）结合并阻止MPO产生HOCl，HOCl是一种强氧化剂，其将导致分子损伤。这两个结果表明，Cp可能是一个重要的抗氧化蛋白在肺衬里液和细胞外间隙。