Crosstalk between CXCR4/stromal derived factor-1 and VLA-4/VCAM-1 pathways regulates neutrophil retention in the bone marrow.
Crosstalk between CXCR4/stromal derived factor-1 and VLA-4/VCAM-1 pathways regulates neutrophil retention in the bone marrow.
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DOI：
10.4049/jimmunol.182.1.604
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发表时间：
2009-01-01
期刊：
影响因子：
--
通讯作者：
Suratt BT
中科院分区：
文献类型：
--
作者：
Petty JM;Lenox CC;Weiss DJ;Poynter ME;Suratt BT
神经元在骨髓中的保留和从骨髓中的释放是一个关键的过程，仍然没有完全理解。先前的研究表明，CXCR 4/SDF-1趋化因子轴参与了中性粒细胞的骨髓滞留，但导致这种滞留的粘附途径尚不清楚。由于α4β1整合素（VLA-4）及其配体VCAM-1在骨髓中造血干细胞、淋巴细胞和发育中的中性粒细胞的相互作用中起核心作用，我们研究了该整合素是否可能参与骨髓中性粒细胞的保留和释放。在这里，我们表明，VLA-4表达的小鼠骨髓中性粒细胞和成熟减少，而这种整合素的封锁导致骨髓中性粒细胞的释放。骨髓嗜中性粒细胞通过VLA-4粘附于在骨髓内皮和基质上表达的VCAM-1，并且VCAM-1的抑制引起骨髓嗜中性粒细胞的释放。此外，SDF-1（CXCL 12）信号通过中性粒细胞CXCR 4增强VLA-4粘附VCAM-1在体外，这是一个效果，被阻断与百日咳毒素预孵育。在体内阻断CXCR 4和α4引起骨髓嗜中性粒细胞的协同释放，表明CXCR 4和VLA-4之间的相互作用调节这些细胞的骨髓滞留。综上所述，这些结果表明，VLA-4/VCAM粘附途径在中性粒细胞从骨髓中的保留和成熟控制释放中至关重要，同时在CXCR 4/SDF-1信号传导轴和控制该过程的粘附事件之间提供了重要的联系。
Neutrophil retention in and release from the bone marrow is a critical process that remains incompletely understood. Previous work has implicated the CXCR4/SDF-1 chemokine axis in the marrow retention of neutrophils, yet the adhesion pathways responsible for this retention are unknown. Since α4β1 integrin (VLA-4) and its ligand VCAM-1 play a central role in the interactions of hematopoietic stem cells, lymphocytes, and developing neutrophils in the marrow, we investigated whether this integrin might be involved in marrow neutrophil retention and release. Here we show that VLA-4 is expressed on murine marrow neutrophils and decreases with maturation, while blockade of this integrin leads to the release of marrow neutrophils. Marrow neutrophils adhere via VLA-4 to VCAM-1, which is expressed on marrow endothelium and stroma, and inhibition of VCAM-1 causes release of marrow neutrophils. Furthermore, SDF-1 (CXCL12) signaling through neutrophil CXCR4 augments VLA-4 adhesion to VCAM-1 in vitro, an effect that is blocked by pre-incubation with pertussis toxin. In vivo blockade of both CXCR4 and α4 causes synergistic release of marrow neutrophils, showing that crosstalk between CXCR4 and VLA-4 modulates marrow retention of these cells. Taken together, these results indicate that the VLA-4/VCAM adhesion pathway is critical in the retention and maturation-controlled release of neutrophils from the marrow, while providing an important link between the CXCR4/SDF-1 signaling axis and the adhesion events that govern this process.
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影响因子：
4.4
作者：
DiVietro, Jeffrey A.;Brown, David C.;Lawrence, Michael B.
通讯作者：
Lawrence, Michael B.
DOI：
10.1073/pnas.92.21.9647
发表时间：
1995-10-10
影响因子：
11.1
作者：
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作者：
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DOI：
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发表时间：
1997-01-06
期刊：
The Journal of experimental medicine
影响因子：
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作者：
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通讯作者：
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影响因子：
30.5
作者：
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