Elimination of senescent neutrophils by TNF-related apopotosis-inducing ligand
Elimination of senescent neutrophils by TNF-related apopotosis-inducing ligand
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DOI：
10.4049/jimmunol.175.2.1232
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发表时间：
2005-07-15
影响因子：
4.4
通讯作者：
Badley, AD
中科院分区：
文献类型：
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作者：
Lum, JJ;Bren, G;Badley, AD
中性粒细胞是吞噬效应细胞，在骨髓中产生并释放到循环中。此后，它们要么被募集到炎症部位，要么迅速衰老，返回骨髓，并经历细胞凋亡。基质细胞衍生因子1（SDF-1）通过与CXCR4相互作用协调衰老中性粒细胞返回骨髓，CXCR4优先表达于衰老中性粒细胞。我们证明，CXCR4连接SDF-1或其他CXCR4激动剂显着增加表达的TNF相关的凋亡诱导配体（TRAIL）和死亡诱导TRAIL受体的中性粒细胞，这赋予了获得性敏感性TRAIL介导的死亡，并导致TRAIL依赖性凋亡。体内施用TRAIL拮抗剂导致骨髓内的嗜中性粒细胞积聚和神经细胞凋亡的减少;相反，重组TRAIL施用减少了骨髓内的神经细胞数量。因此，CXCR4的SDF-1连接导致趋化性和增强的TRAIL和TRAIL死亡受体表达的平行过程，导致衰老的中性粒细胞在返回骨髓时凋亡。
Neutrophils are phagocytic effectors which are produced in the bone marrow and released into the circulation. Thereafter, they are either recruited to sites of inflammation or rapidly become senescent, return to the bone marrow, and undergo apoptosis. Stromal cell-derived factor 1 (SDF-1) coordinates the return of senescent neutrophils to the bone marrow by interacting with CXCR4 that is preferentially expressed on senescent nentrophils. We demonstrate that CXCR4 ligation by SDF-1 or other CXCR4 agonists significantly increases the expression of both TNF-related apopotosis-inducing ligand (TRAIL) and of the death-inducing TRAIL receptors on neutrophils, which confers an acquired sensitivity to TRAIL-mediated death and results in TRAIL-dependent apoptosis. In vivo administration of TRAIL antagonists results in neutrophilic accumulation within the bone marrow and a reduction in nentrophil apoptosis; conversely recombinant TRAIL administration reduced nentrophil number within bone marrow. Thus, SDF-1 ligation of CXCR4 causes the parallel processes of chemotaxis and enhanced TRAIL and TRAIL death receptor expression, resulting in apoptosis of senescent neutrophils upon their return to the bone marrow.