Engagement of the Lewis X antigen (CD15) results in monocyte activation
Engagement of the Lewis X antigen (CD15) results in monocyte activation
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DOI：
10.1182/blood.v89.1.307.307_307_314
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发表时间：
1997-01-01
期刊：
影响因子：
20.3
通讯作者：
Silverstein, RL
中科院分区：
文献类型：
--
作者：
Lo, SK;Golenbock, DT;Silverstein, RL
我们之前报道过单核细胞粘附在肿瘤坏死因子- α (tnf - α)处理的内皮细胞上增加了单核细胞上组织因子和CD36的表达。利用免疫交联模拟天然配体的受体参与，我们现在表明CD15 (Lewis X)，内皮选择素的单核细胞对抗受体可能参与这种反应。我们使用细胞因子产生作为单核细胞激活的读数，发现CD15交联诱导外周血单核细胞和单核细胞系MM6细胞释放tnf - α。定量逆转录聚合酶链反应（RT-PCR）显示，交联3 ~ 4小时后，稳态tnf - α mRNA增加。CD15交联还同时增加了白细胞介素-1 β (IL-1 β) mRNA，而β -肌动蛋白mRNA水平未见明显变化，表明特异性。为了研究CD15参与对细胞因子基因的转录调控，将含有IL-1 β启动子/增强子序列的CAT质粒报告结构引入MM6。随后的CD15交联增加了CAT活性。单克隆抗体与CD15的结合也减弱了IL-1 β转录物的降解，表明通过CD15的信号传导也具有转录后效应。抗cd15交联细胞的核提取物显示转录因子激活蛋白-1的水平增加，核因子- κ B的变化最小，并且不影响SV40启动子特异性蛋白-1。我们得出结论，CD15与单核细胞的结合导致单核细胞活化。除了其众所周知的粘附作用外，CD15可能作为一种重要的信号分子，能够在与活化的内皮细胞接触的单核细胞中启动促炎事件。(C) 1997年由美国血液病学会出版。
We previously reported that monocyte adhesion to tumor necrosis factor-alpha (TNF-alpha)-treated endothelial cells increased expression of tissue factor and CD36 on monocytes. Using immunological cross-linking to mimic receptor engagement by natural ligands, we now show that CD15 (Lewis X), a monocyte counter-receptor for endothelial selectins may participate in this response. We used cytokine production as a readout for monocyte activation and found that CD15 cross-linking induced TNF-alpha release from peripheral blood monocytes and cells from the monocytic cell line MM6. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) showed an increase in steady-state TNF-alpha mRNA after 3 to 4 hours of cross-linking. CD15 cross-linking also concomitantly increased interleukin-1 beta (IL-1 beta) mRNA, while no apparent change was observed in the levels of beta-actin mRNA, indicating specificity. To examine transcriptional regulation of cytokine genes by CD15 engagement, a CAT plasmid reporter construct containing IL-1 beta promoter/enhancer sequences was introduced into MM6. Subsequent cross-linking of CD15 increased CAT activity. CD15 engagement by monoclonal antibody also attenuated IL-1 beta transcript degradation, demonstrating that signaling via CD15 also had posttranscriptional effects. Nuclear extracts of anti-CD15 cross-linked cells demonstrated enhanced levels of the transcriptional factor activator protein-1, minimally changed nuclear factor-kappa B, and did not affect SV40 promoter specific protein-1. We conclude that engagement of CD15 on monocytes results in monocyte activation. In addition to its well-recognized adhesive role, CD15 may function as an important signaling molecule capable of initiating proinflammatory events in monocytes that come into contact with activated endothelium. (C) 1997 by The American Society of Hematology.