UP-REGULATION OF INTEGRINS ALPHA-V-BETA-3 AND ALPHA-V-BETA-5 ON HUMAN MONOCYTES AND T-LYMPHOCYTES FACILITATES ADENOVIRUS-MEDIATED GENE DELIVERY
UP-REGULATION OF INTEGRINS ALPHA-V-BETA-3 AND ALPHA-V-BETA-5 ON HUMAN MONOCYTES AND T-LYMPHOCYTES FACILITATES ADENOVIRUS-MEDIATED GENE DELIVERY
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DOI：
10.1128/jvi.69.4.2257-2263.1995
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发表时间：
1995-04-01
影响因子：
5.4
通讯作者：
NEMEROW, GR
中科院分区：
文献类型：
--
作者：
HUANG, SA;ENDO, RI;NEMEROW, GR
人腺病毒进入宿主细胞涉及病毒颗粒与两种不同受体的相互作用，最初的结合事件是由纤维蛋白介导的，而随后五邻体基础蛋白与αv整合素的相互作用促进病毒内化和/或渗透。虽然上皮细胞和内皮细胞中的这些相互作用已被充分表征，但对于这些事件是否发生在病毒感染人外周血单核细胞期间知之甚少。我们证明新鲜分离的外周血单核细胞和T淋巴细胞表达非常少量单核细胞暴露于造血生长因子、粒细胞-巨噬细胞集落刺激因子和巨噬细胞集落刺激因子诱导细胞表面αv整合素的表达，促进五邻体碱基蛋白的结合，并且还使这些细胞对腺病毒介导的基因传递敏感，用促细胞分裂剂、植物血凝素或细胞活化剂佛波醇肉豆蔻酸酯乙酸酯诱导αv整合素的表达并增强腺病毒介导的基因递送。这些研究进一步表明αv整合素在腺病毒感染中发挥着至关重要的作用，并且还为增强腺病毒介导的基因递送至人外周血单核细胞中提供了有用的策略。
Entry of human adenovirus into host cells involves interaction of virus particles with two distinct receptors, The initial binding event is mediated by the fiber protein, while subsequent interaction of the penton base protein with alpha v integrins promotes virus internalization and/or penetration, Although these interactions in epithelial and endothelial cells have been well characterized, relatively little is known as to whether these events occur during virus infection of human peripheral blood mononuclear cells, We demonstrate that freshly isolated peripheral blood monocytes and T lymphocytes express very small amounts of alpha v integrins and also are resistant to adenovirus infection, Exposure of monocytes to hematopoietic growth factors granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor induced expression of cell surface alpha v integrins, promoted the binding of penton base protein, and also rendered these cells susceptible to adenovirus-mediated gene delivery, Stimulation of T cells with a mitogen, phytohemagglutinin, or a cell-activating agent, phorbol myristate acetate, induced expression of alpha v integrins and also enhanced adenovirus-mediated gene delivery, These studies further indicate that alpha v integrins play a crucial role in adenovirus infection and also provide a useful strategy for enhancing adenovirus-mediated gene delivery into human peripheral blood mononuclear cells.