Mac-1 (CDllb/CD18) is an oligodeoxynucleotide-binding protein
Mac-1 (CDllb/CD18) is an oligodeoxynucleotide-binding protein
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DOI：
10.1038/nm0497-414
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发表时间：
1997-04-01
期刊：
影响因子：
82.9
通讯作者：
Stein, CA
中科院分区：
文献类型：
--
作者：
Benimetskaya, L;Loike, JD;Stein, CA
我们研究了磷酸二酯和硫代寡核苷酸与Mac-1(CD11b/CD18；αMβ2)的相互作用，Mac-1是一种主要存在于多形核白细胞(PMN)、巨噬细胞和自然杀伤细胞表面的肝素结合整合素。胸腺嘧啶核苷均聚体结合在αM和β2亚基上。可溶性纤维蛋白原是Mac-1的天然配体，是硫代寡核苷酸与肿瘤坏死因子α激活和非激活的PMN结合的有力竞争者。细胞表面Mac-1表达上调增加了寡核苷酸与细胞表面的结合。结合被抗Mac-1的单抗抑制，细胞表面结合的增加与PMN内化的三到四倍有关。一种寡聚脱氧核苷酸抑制β2依赖的通过Matrigel的迁移，但附着于纤维蛋白原的PMN中的活性氧物种的产生显著增加。因此，我们的数据表明，Mac-1是寡聚脱氧核苷酸的细胞表面受体，可以介导其内化，这种结合可能具有重要的功能后果。
We have studied the interactions of phosphodiester and phosphorothioate oligodeoxynucleotides with Mac-1 (CD11b/CD18; alpha M beta 2), a heparin-binding integrin found predominately on the surface of polymorphonuclear leukocytes (PMNs), macrophages and natural killer cells. Binding of a homopolymer of thymidine occurred on both the alpha M and beta 2 subunits. Soluble fibrinogen, a natural ligand for Mac-1, was an excellent competitor of the binding of a phosphorothioate oligodeoxynucleotide to both TNF-alpha-activated and nonactivated PMNs. Upregulation of cell-surface Mac-1 expression increased cell-surface binding of oligodeoxynucleotides. Binding was inhibited by anti-Mac-1 monoclonal antibodies, and the increase in cell-surface binding was correlated with a three- to fourfold increase in internalization by PMNs. An oligodeoxynucleotide inhibited beta 2-dependent migration through Matrigel, but the production of reactive oxygen species in PMNs adherent to fibrinogen dramatically increased. Thus, our data demonstrate that Mac-1 is a cell-surface receptor for oligodeoxynucleotides that can mediate their internalization and that this binding may have important functional consequences.