Clearance of oxidatively damaged cells by macrophages: recognition of glycoprotein clusters by macrophage-surface nucleolin as early apoptotic cells.-猫眼课题宝

巨噬细胞清除氧化损伤的细胞：巨噬细胞表面核仁蛋白将糖蛋白簇识别为早期凋亡细胞。

DOI：

发表时间：

2009

期刊：

Biological and Pharmaceutical Bulletin

影响因子：

通讯作者：

中科院分区：

医学4区

文献类型：

作者：

Y. Miki;T. Itoh;K. Hirano;S. Eda;Akiko Hayashi;M. Yamanaka;M. Beppu

探讨了巨噬细胞识别氧化损伤细胞的机制。Jurkat T细胞暴露于不同浓度的H（2）O（2）后被巨噬细胞结合并吞噬。暴露于0.1 mM H（2）O（2）的细胞结合最好。巨噬细胞识别的细胞表面配体可能是唾液酸糖蛋白CD 43的唾液酸聚乳糖胺糖链，因为1）含唾液酸聚乳糖胺糖链的寡糖抑制细胞结合，其抑制活性被聚乳糖胺裂解酶内切-β-半乳糖苷酶和神经氨酸酶破坏; 2）用糖苷酶或抗CD 43抗体预处理的氧化Jurkat细胞不被结合。参与结合的巨噬细胞受体被认为是细胞表面核仁素，因为1）抗核仁素抗体抑制结合; 2）核仁素转染的HEK 293细胞结合氧化细胞; 3）这种结合被抗核仁素抗体和抗CD 43抗体抑制。氧化的Jurkat细胞上的CD 43倾向于形成簇，这与它们对巨噬细胞结合的敏感性良好一致。CD 43聚集和氧化细胞与巨噬细胞的结合被半胱天冬酶抑制剂Z-VAD-favor阻止，表明氧化和结合的细胞正在经历凋亡。事实上，Jurkat细胞的caspase-3活性通过氧化而增加。这些结果表明，中度氧化的细胞发生凋亡，并被巨噬细胞识别为早期凋亡细胞。

The mechanism of macrophage recognition of oxidatively damaged cells was investigated. Jurkat T cells exposed to various concentrations of H(2)O(2) were bound and phagocytosed by macrophages. The cells exposed to 0.1 mM H(2)O(2) were best bound. The cell-surface ligands recognized by macrophages were suggested to be sialylpolylactosaminyl sugar chains of a major sialoglycoprotein CD43 because 1) the cell binding was inhibited by oligosaccharides containing sialylpolylactosaminyl chains, and their inhibitory activity was destroyed by a polylactosamine-cleaving enzyme endo-beta-galactosidase, and by neuraminidase; 2) the oxidized Jurkat cells pretreated with either glycosidase or with anti-CD43 antibody were not bound. The macrophage receptor involved in the binding was suggested to be cell-surface nucleolin because 1) anti-nucleolin antibody inhibited the binding; 2) nucleolin-transfected HEK293 cells bound the oxidized cells; and 3) this binding was inhibited by anti-nucleolin antibody and by anti-CD43 antibody. CD43 on oxidized Jurkat cells tended to form clusters in good accordance with their susceptibility to the macrophage binding. CD43 clustering and the oxidized-cell binding to macrophages were prevented by a caspase inhibitor Z-VAD-fmk, suggesting that the oxidized and bound cells were undergoing apoptosis. Indeed, caspase-3 activity of Jurkat cells increased by the oxidation. These results suggest that moderately oxidized cells undergo apoptosis and are recognized by macrophages as early apoptotic cells.

Macrophages lacking scavenger receptor A show a decrease in binding and uptake of acetylated low-density lipoprotein and of apoptotic thymocytes, but not of oxidatively damaged red blood cells.